BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming...BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming a specific type of ubiquitin ligase subunit,which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer.Never-theless,the function of FBXO22 in the context of colon cancer remains inade-quately elucidated.AIM To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.METHODS Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered,along with pertinent clinical data.Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immu-nohistochemistry.The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues,and the relationship between these expression levels and various pathologic character-istics of patients,such as age,sex,and clinical stage,was analyzed.Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups:A blank control group,a negative control group,and a si-FBXO22 group.FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting.The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay,while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays.Various online platforms,including the Timer Immune Estimation Resource,were used to analyze pan-cancer expression,promoter methylation levels,and mutation frequencies of the FBXO22 gene in colon cancer patients.Additionally,the correlation between FBXO22 gene expression,patient prognosis,immune cell infiltration,and the expression of immune molecules in the colon cancer microenvironment was investigated.The relationship between FBXO22 gene expression and chemotherapy resistance,along with the potential mechanisms of action of the FBXO22 gene,were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.RESULTS Compared with normal colonic tissues,the FBXO22 gene was highly expressed in colon cancer tissues.Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents.FBXO22 expression suppresses the infiltration of anti-tumor immune cells.In vitro,FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.CONCLUSION The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.展开更多
F-box protein is an expanding family member of eukaryotic protein characterized by an F-box motif which has specificity of substrate recognition in the ubiquitin-mediated proteolysis.These proteins have been proved to...F-box protein is an expanding family member of eukaryotic protein characterized by an F-box motif which has specificity of substrate recognition in the ubiquitin-mediated proteolysis.These proteins have been proved to be critical for many physiological processes,such as cell-cycle transition,signal transduction,gene transcription,male sterility,programmed cell death （PCD） and so on.This paper mainly introduces the biological functions of the known F-box proteins and the analysis of F-box gene phylogeny.展开更多
Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest ...Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest for concentrated fruit set and higher densities（Li et al.,2011;Mondal et al.,2011）.展开更多
In flowering plants, self-incompatibility （SI） serves as an important intraspecific reproductive barrier to promote outbreeding. In species from the Solanaceae, Plantaginaceae and Rosaceae, S-RNase and SLF （S-locus...In flowering plants, self-incompatibility （SI） serves as an important intraspecific reproductive barrier to promote outbreeding. In species from the Solanaceae, Plantaginaceae and Rosaceae, S-RNase and SLF （S-locus F-box） proteins have been shown to control the female and male specificity of SI, respectively. However, little is known about structure features of the SLF protein apart from its conserved F-box domain. Here we show that the SLF C-terminal region possesses a novel ubiquitin-binding domain （UBD） structure conserved among the SLF protein family. By using an ex vivo system of Nicotiana benthamiana, we found that the UBD mediates the SLF protein turnover by the ubiquitin-proteasome pathway. Furthermore, we detected that the SLF protein was directly involved in S-RNase degradation. Taken together, our results provide a novel insight into the SLF structure and highlight a potential role of SLF protein stability and degradation in S-RNase-based self-incompatibility.展开更多
Estrogens are accumulating in environment and their effects on a variety of reproductive processes and tumorigenesis were reported by previous study,but the mechanism of estrogen promoting neoplasia was still not clea...Estrogens are accumulating in environment and their effects on a variety of reproductive processes and tumorigenesis were reported by previous study,but the mechanism of estrogen promoting neoplasia was still not clear.F-box protein(FBP)is the component of E3 ubiquitin ligase which takes part in a variety of key biological processes.In this study,using mature male zebrafish,which are more sensitive to estrogen treatment,we examined influence of 17α-ethinylestradiol(EE2)exposure on the expression of a series of hepatic FBP genes,which take part in a variety of biological processes,including tumorigenesis.The influence of EE2 on the expression of hepatic mRNA concentrations of FBP genes were quantified based on the expression of the optimal internal control gene in male zebrafish after 7-day exposure to EE2,from a low-dose concentration(1 ng/L)to environmentally relevant concentrations(10,100 ng/L).Our results showed that EE2 exposure reduced the expression of fbxl14a,fbxl14b,fbxo25 andβ-TRCP2b,but enchanced the expression of skp2.While the alterations in fbxl2,fbxw7,fbxo9,β-TRCP2a,fbxl18 and fbxo45 mRNA levels were not observed after EE2 exposure.Thus,our results showed that the expression of hepatic FBP genes exhibited differentially in male zebrafish exposed EE2.The changes of the expression level of FBP genes induced by EE2 may be an important clue to elucidate the correlations of estrogen and hepatic tumors.展开更多
Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,wi...Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.展开更多
With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacin...With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.展开更多
The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR...The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.展开更多
α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at mu...Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin-proteasome system （UPS）, which consists of two distinct steps： （1） ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and （2） subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF （SKP1-CUL1-F-box protein） E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.展开更多
Root meristem activity is essential for root morphogenesis and adaptation,but the molecular mechanism regulating root meristem activity is not fully understood.Here,we identify an F-box family E3 ubiquitin ligase name...Root meristem activity is essential for root morphogenesis and adaptation,but the molecular mechanism regulating root meristem activity is not fully understood.Here,we identify an F-box family E3 ubiquitin ligase named SHORT PRIMARY ROOT(SHPR) that regulates primary root(PR)meristem activity and cell proliferation in rice.SHPR loss-of-function mutations impair PR elongation in rice.SHPR is involved in the formation of an SCF complex with the Oryza sativa SKP1-like protein OSK1/20.We show that SHPR interacts with Oryza sativa SEUSS-LIKE(OsSLK) in the nucleus and is required for OsSLK polyubiquitination and degradation by the ubiquitin 26S-proteasome system(UPS).Transgenic plants overexpressing OsSLK display a shorter PR phenotype,which is similar to the SHPR loss-of-function mutants.Genetic analysis suggests that SHPR promotes PR elongation in an OsSLK-dependent manner.Collectively,our study establishes SHPR as an E3 ubiquitin ligase that targets OsSLK for degradation,and uncovers a protein ubiquitination pathway as a mechanism for modulating root meristem activity in rice.展开更多
F-box proteins play essential roles in various cellular processes of spermatogenesis by means of ubiquitylation and subsequent target protein degradation.They are the substrate-recognition subunits of SKP1–cullin 1–...F-box proteins play essential roles in various cellular processes of spermatogenesis by means of ubiquitylation and subsequent target protein degradation.They are the substrate-recognition subunits of SKP1–cullin 1–F-box protein(SCF)E3 ligase complexes.Dysregulation of F-box protein-mediated proteolysis could lead to male infertil-ity in humans and mice.The emerging studies revealed the physiological function,pathological evidence,and bio-chemical substrates of F-box proteins in the development of male germ cells,which urging us to review the current understanding of how F-box proteins contribute to spermatogenesis.More functional and mechanistic study will be helpful to define the roles of F-box protein in spermatogenesis,which will pave the way for the logical design of F-box protein-targeted diagnosis and therapies for male infertility,as the spermatogenic role of many F-box proteins remains elusive.展开更多
In eukaryotes, the ubiquitin-mediated protein degradation pathway has been shown to control several key biological processes such as cell division, development, metabolism and immune response. F-box proteins, as a par...In eukaryotes, the ubiquitin-mediated protein degradation pathway has been shown to control several key biological processes such as cell division, development, metabolism and immune response. F-box proteins, as a part of SCF (Skp1-Cullin (or Cdc53)-F-box) complex, functioned by interacting with substrate proteins, leading to their subsequent degradation by the 26S proteasome. To date, several F-box proteins identified in Arabidopsis and Antirrhinum have been shown to play important roles in auxin signal transduction, floral organ formation, flowering and leaf senescence. Arabidopsis genome sequence analysis revealed that it encodes over 1000 predicted F-box proteins accounting for about 5% of total predicted proteins. These results indicate that the ubiquitin-mediated protein degradation involving the F-box proteins is an important mechanism controlling plant gene expression. Here, we review the known F-box proteins and their functions in flowering plants.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive...BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。展开更多
As one of the largest gene families, F-box domain proteins have important roles in regulating various devel- opmental processes and stress responses. In this study, we have investigated a rice F-box domain gene, MAIF1...As one of the largest gene families, F-box domain proteins have important roles in regulating various devel- opmental processes and stress responses. In this study, we have investigated a rice F-box domain gene, MAIF1. The MAIF1 protein is mainly localized in the plasma membrane and nucleus. MAIF1 expression is induced rapidly and strongly by abscisic acid （ABA） and abiotic stresses. MAIF1 expression is also induced in root tips by sucrose, independent of its hy- drolytic hexose products, glucose and fructose, and the plant hormones auxin and cytokinin. Overexpression of MAIF1 reduces rice ABA sensitivity and abiotic stress tolerance and promotes rice root growth. These results suggest that MAIF1 is involved in multiple signaling pathways in regulating root growth. Growth restraint in plants is an acclimatization strategy against abiotic stress, Our results also suggest that MAIF1 plays the negative role in response to abiotic stress possibly by regulating root growth.展开更多
Gibberellins(GAs)play important roles in multiple developmental processes and in plant response to the environment.Within the GA pathway,a central regulatory step relies on GA-dependent degradation of the DELLA transc...Gibberellins(GAs)play important roles in multiple developmental processes and in plant response to the environment.Within the GA pathway,a central regulatory step relies on GA-dependent degradation of the DELLA transcriptional regulators.Nevertheless,the relevance of the stability of other key proteins in this pathway,such as SLY1 and SNE(the F-box proteins involved in DELLA degradation),remains unknown.Here,we take advantage of mutants in the HSP70-HSP90 organizing protein(HOP)co-chaperones and reveal that these proteins contribute to the accumulation of SNE in Arabidopsis.Indeed,HOP proteins,along with HSP90 and HSP70,interact in vivo with SNE,and SNE accumulation is significantly reduced in the hop mutants.Concomitantly,greater accumulation of the DELLA protein RGA is observed in these plants.In agreement with these molecular phenotypes,hop mutants show a hypersensitive response to the GA inhibitor paclobutrazol and display a partial response to the ectopic addition of GA when GA-regulated processes are assayed.These mutants also display different phenotypes associated with alterations in the GA pathway,such as reduced germination rate,delayed bolting,and reduced hypocotyl elongation in response to warm temperatures.Remarkably,ectopic overexpression of SNE reverts the delay in germination and the thermally dependent hypocotyl elongation defect of the hop1 hop2 hop3 mutant,revealing that SNE accumulation is the key aspect of the hop mutant phenotypes.Together,these data reveal a pivotal role for HOP in SNE accumulation and GA signaling.展开更多
Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of t...Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.展开更多
基金The study was reviewed and approved by institutional ethics board of Affiliated Hospital of Hebei Engineering University(No.:2024[K]005-01).
文摘BACKGROUND Colon cancer represents a significant malignant neoplasm within the digestive system,characterized by a high incidence rate and substantial disease burden.The F-box protein 22(FBXO22)plays a role in forming a specific type of ubiquitin ligase subunit,which is expressed abnormally in various malignant neoplasms and shows a notable relationship with prognosis in patients with cancer.Never-theless,the function of FBXO22 in the context of colon cancer remains inade-quately elucidated.AIM To explore the role of FBXO22 in colon cancer by examining FBXO22 expression patterns and analyzing how the protein affects the prognosis in patients who have undergone surgery.METHODS Samples of cancerous and nearby normal tissues from patients with colon cancer were gathered,along with pertinent clinical data.Expression levels of the FBXO22 gene in both cancerous and paracancerous tissues were assessed through immu-nohistochemistry.The median H score served as a criterion for categorizing FBXO22 gene expression into high and low levels in cancerous tissues,and the relationship between these expression levels and various pathologic character-istics of patients,such as age,sex,and clinical stage,was analyzed.Colon cancer cell lines HCT116 and DLD-1 were used and divided into three groups:A blank control group,a negative control group,and a si-FBXO22 group.FBXO22 gene mRNA and protein expression were measured 24 hours post-transfection using real-time fluorescence quantitative polymerase chain reaction and western blotting.The proliferation capabilities of the cells in each group were assessed using the Cell Counting Kit-8 assay and 5-ethynyl-2’-deoxyuridine assay,while cellular migration and invasion abilities were evaluated using scratch healing and Transwell assays.Various online platforms,including the Timer Immune Estimation Resource,were used to analyze pan-cancer expression,promoter methylation levels,and mutation frequencies of the FBXO22 gene in colon cancer patients.Additionally,the correlation between FBXO22 gene expression,patient prognosis,immune cell infiltration,and the expression of immune molecules in the colon cancer microenvironment was investigated.The relationship between FBXO22 gene expression and chemotherapy resistance,along with the potential mechanisms of action of the FBXO22 gene,were analyzed using The Cancer Genome Atlas dataset and the Genomics of Drug Sensitivity in Cancer drug training set via R software.RESULTS Compared with normal colonic tissues,the FBXO22 gene was highly expressed in colon cancer tissues.Post-operative patients with colon cancer elevated FBXO22 reduced survival and exhibited resistance to various chemotherapeutic agents.FBXO22 expression suppresses the infiltration of anti-tumor immune cells.In vitro,FBXO22 knockdown inhibited the proliferation and migration of colon cancer cells.CONCLUSION The FBXO22 gene is a biomarker of poor prognosis in patients with colon cancer and has potential as a target for immunotherapy and overcoming chemotherapy resistance.
基金Supported by the Cloning and Genetics Analysis of Cold-Induced Genes in PA64S, Natural Science Foundation of Hunan Province(09JJ3044)
文摘F-box protein is an expanding family member of eukaryotic protein characterized by an F-box motif which has specificity of substrate recognition in the ubiquitin-mediated proteolysis.These proteins have been proved to be critical for many physiological processes,such as cell-cycle transition,signal transduction,gene transcription,male sterility,programmed cell death （PCD） and so on.This paper mainly introduces the biological functions of the known F-box proteins and the analysis of F-box gene phylogeny.
基金supported by funding from the National Natural Science Foundation of China(No.31225025)the National Basic Research Program of China(973 Program) (No.2012CB113900)+3 种基金the National High-tech R&D Program (863 Program)(No.2012AA100101)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-AGISCAAS)the leading talents of Guangdong province Program(No. 00201515)supported by the Shenzhen Municipal and Dapeng District governments
文摘Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest for concentrated fruit set and higher densities（Li et al.,2011;Mondal et al.,2011）.
基金supported by the National Basic Research Program of China(973 Program)(Nos.2007CB108703 and 2011CB915404)the National Natural Science Foundation of China(No.30921003)
文摘In flowering plants, self-incompatibility （SI） serves as an important intraspecific reproductive barrier to promote outbreeding. In species from the Solanaceae, Plantaginaceae and Rosaceae, S-RNase and SLF （S-locus F-box） proteins have been shown to control the female and male specificity of SI, respectively. However, little is known about structure features of the SLF protein apart from its conserved F-box domain. Here we show that the SLF C-terminal region possesses a novel ubiquitin-binding domain （UBD） structure conserved among the SLF protein family. By using an ex vivo system of Nicotiana benthamiana, we found that the UBD mediates the SLF protein turnover by the ubiquitin-proteasome pathway. Furthermore, we detected that the SLF protein was directly involved in S-RNase degradation. Taken together, our results provide a novel insight into the SLF structure and highlight a potential role of SLF protein stability and degradation in S-RNase-based self-incompatibility.
基金supported by the Major State Basic Research Development Program(973)of China(No.2007CB947100)the Shanghai Municipal Commission for Science and Technology(No.074319111,07DZ22919).
文摘Estrogens are accumulating in environment and their effects on a variety of reproductive processes and tumorigenesis were reported by previous study,but the mechanism of estrogen promoting neoplasia was still not clear.F-box protein(FBP)is the component of E3 ubiquitin ligase which takes part in a variety of key biological processes.In this study,using mature male zebrafish,which are more sensitive to estrogen treatment,we examined influence of 17α-ethinylestradiol(EE2)exposure on the expression of a series of hepatic FBP genes,which take part in a variety of biological processes,including tumorigenesis.The influence of EE2 on the expression of hepatic mRNA concentrations of FBP genes were quantified based on the expression of the optimal internal control gene in male zebrafish after 7-day exposure to EE2,from a low-dose concentration(1 ng/L)to environmentally relevant concentrations(10,100 ng/L).Our results showed that EE2 exposure reduced the expression of fbxl14a,fbxl14b,fbxo25 andβ-TRCP2b,but enchanced the expression of skp2.While the alterations in fbxl2,fbxw7,fbxo9,β-TRCP2a,fbxl18 and fbxo45 mRNA levels were not observed after EE2 exposure.Thus,our results showed that the expression of hepatic FBP genes exhibited differentially in male zebrafish exposed EE2.The changes of the expression level of FBP genes induced by EE2 may be an important clue to elucidate the correlations of estrogen and hepatic tumors.
基金financially supported by the Hainan Province Science and Technology Special Fund(Grant no:ZDYF2024XDNY187).
文摘Background:Excessive use of inorganic trace minerals(ITMs)in swine production leads to high fecal mineral excretion and environmental risks,while most studies on organic trace minerals(OTMs)focus on single elements,with limited data on the synergistic effects and molecular mechanisms of combined OTMs(Fe,Cu,Mn,Zn)in growing-finishing pigs.Methods:This study aimed to investigate the effects of graded levels of micromineral proteinates(combined OTMs)on growth performance,mineral metabolism,and mRNA expression of mineral regulatory proteins.A total of 360 crossbred Duroc×Landrace×Large White pigs(initial body weight 47.1±4.8 kg)were randomly assigned to 6 dietary treatments:basal diet without microminerals(CON),basal diet with ITMs at commercially recommended levels(IT),and basal diets with 15%(OT 15%),25%(OT 25%),35%(OT 35%)commercially recommended levels(CRL)of combined micromineral proteinates.After a 70-day feeding trial,samples were analyzed using ICP-OES,ELISA,and RT-qPCR.Results:Results showed that reduced levels(15-35%CRL)of micromineral proteinates did not significantly affect average daily gain,average daily feed intake,or feed conversion ratio(gain-to-feed ratio)compared to IT(P>0.05),but significantly increased plasma Cu(1.73-1.83μg/mL)and Zn(1.72-1.97μg/mL)concentrations(P<0.05)and elevated activities of Cu/Zn-superoxide dismutase(32.9-35.9 U/L)and manganese superoxide dismutase(20.5-24.1 U/L)compared to CON(P<0.05),with no significant differences from IT(P>0.05).Fecal excretion of Fe,Cu,Mn,and Zn was significantly reduced by 35-50%in OT 15%-OT 35%groups compared to IT(P<0.05).OT 25%group exhibited the highest apparent absorptivity of Fe(38.5%),Cu(27.8%),and Zn(42.4%)(P<0.05),which was associated with significantly regulated mRNA expression of mineral regulatory proteins:upregulated DMT1,FPN1,ZIP4,and MT1A in the duodenum,and modulated HAMP,ATP7B,ZIP14,and ZnT1 in the liver(P<0.05).Conclusion:In conclusion,dietary supplementation with 25%CRL or less of combined micromineral proteinates can fully meet the nutritional needs of growing-finishing pigs,improve mineral absorptivity,and reduce fecal mineral excretion by regulating intestinal and hepatic mineral transport and homeostatic proteins,providing a sustainable alternative to high-dose ITMs.
文摘With the growth of global protein demand and the development of plant-based foods,pea protein,as a low-allergenic,nutritionally balanced and environmentally friendly plant protein,has shown great potential in replacing animal protein.Pea protein is mainly composed of globulin and albumin,with a protein content of 20%to 30%,and has a balanced amino acid composition,as well as being rich in minerals and dietary fiber.It also possesses good foaming,gelling,emulsifying and antioxidant functional properties.However,pea protein also has inherent defects that limit its application in the food industry.This article systematically reviews the extraction techniques,functional properties,modification methods and application fields of pea protein,and focuses on evaluating the effects of different extraction and modification strategies on protein yield and functional properties.Research shows that ultrasonic-assisted alkaline extraction can reduce solvent usage by 55%,shorten extraction time by 50%,and increase extraction rate by 12.51%;under optimized conditions,ultrafiltration membrane technology can achieve a protein purity of 91%.In terms of modification,ultrasonic treatment increases foaming capacity by 37.4%,and phenolic cross-linking increases gel strength from 3.0 kPa to 48 kPa.This article provides data support and theoretical reference for the efficient extraction and functional optimization of pea protein,and has promoting significance for its wide application in plant-based foods.
基金the National Natural Science Foundation of China(82573571)the Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13)。
文摘The global burden of bacterial infections,exacerbated by antimicrobial resistance(AMR),necessitates innovative strategies.Bacterial protein vaccines offer promise by eliciting targeted immunity while circumventing AMR.However,their clinical translation is hindered by their inherently low immunogenicity,often requiring potent adjuvants and advanced delivery systems.Biomembrane nanostructures(e.g.,liposomes,exosomes,and cell membrane-derived nanostructures),characterized by superior biocompatibility,intrinsic targeting ability,and immune-modulating properties,could serve as versatile platforms that potentiate vaccine efficacy by increasing antigen stability,enabling codelivery of immunostimulants,and facilitating targeted delivery to lymphoid tissues/antigen-presenting cells.This intrinsic immunomodulation promotes robust humoral and cellular immune responses to combat bacteria.This review critically reviews(1)key biomembrane nanostructure classes for bacterial protein antigens,(2)design strategies leveraging biomembrane nanostructures to enhance humoral and cellular immune responses,(3)preclinical efficacy against diverse pathogens,and(4)translational challenges and prospects.Biomembrane nanostructure-driven approaches represent a paradigm shift in the development of next-generation bacterial protein vaccines against resistant infections.
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the National Cancer Institute grants (Nos. CA118762, CA156744, CA170995 and CA171277) to Y.Sthe National Institute of General Medical Sciences grant (No. GM094777) to W.W
文摘Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin-proteasome system （UPS）, which consists of two distinct steps： （1） ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and （2） subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF （SKP1-CUL1-F-box protein） E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.
基金supported by grants from the National Natural Science Foundation of China (31671516 and 31970806)。
文摘Root meristem activity is essential for root morphogenesis and adaptation,but the molecular mechanism regulating root meristem activity is not fully understood.Here,we identify an F-box family E3 ubiquitin ligase named SHORT PRIMARY ROOT(SHPR) that regulates primary root(PR)meristem activity and cell proliferation in rice.SHPR loss-of-function mutations impair PR elongation in rice.SHPR is involved in the formation of an SCF complex with the Oryza sativa SKP1-like protein OSK1/20.We show that SHPR interacts with Oryza sativa SEUSS-LIKE(OsSLK) in the nucleus and is required for OsSLK polyubiquitination and degradation by the ubiquitin 26S-proteasome system(UPS).Transgenic plants overexpressing OsSLK display a shorter PR phenotype,which is similar to the SHPR loss-of-function mutants.Genetic analysis suggests that SHPR promotes PR elongation in an OsSLK-dependent manner.Collectively,our study establishes SHPR as an E3 ubiquitin ligase that targets OsSLK for degradation,and uncovers a protein ubiquitination pathway as a mechanism for modulating root meristem activity in rice.
基金National Natural Science Foundation of China(82371627)Open Research Fund of Key Laboratory of Reproductive Medicine of Guangdong Province(2020B121206002902)+1 种基金Natural Science Foundation of Fujian Province(2021J011346)Xiamen Medical and Health Guidance Project(3502Z20244ZD1021).
文摘F-box proteins play essential roles in various cellular processes of spermatogenesis by means of ubiquitylation and subsequent target protein degradation.They are the substrate-recognition subunits of SKP1–cullin 1–F-box protein(SCF)E3 ligase complexes.Dysregulation of F-box protein-mediated proteolysis could lead to male infertil-ity in humans and mice.The emerging studies revealed the physiological function,pathological evidence,and bio-chemical substrates of F-box proteins in the development of male germ cells,which urging us to review the current understanding of how F-box proteins contribute to spermatogenesis.More functional and mechanistic study will be helpful to define the roles of F-box protein in spermatogenesis,which will pave the way for the logical design of F-box protein-targeted diagnosis and therapies for male infertility,as the spermatogenic role of many F-box proteins remains elusive.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39825103)the Chinese Academy of Sciences.
文摘In eukaryotes, the ubiquitin-mediated protein degradation pathway has been shown to control several key biological processes such as cell division, development, metabolism and immune response. F-box proteins, as a part of SCF (Skp1-Cullin (or Cdc53)-F-box) complex, functioned by interacting with substrate proteins, leading to their subsequent degradation by the 26S proteasome. To date, several F-box proteins identified in Arabidopsis and Antirrhinum have been shown to play important roles in auxin signal transduction, floral organ formation, flowering and leaf senescence. Arabidopsis genome sequence analysis revealed that it encodes over 1000 predicted F-box proteins accounting for about 5% of total predicted proteins. These results indicate that the ubiquitin-mediated protein degradation involving the F-box proteins is an important mechanism controlling plant gene expression. Here, we review the known F-box proteins and their functions in flowering plants.
基金the National Natural Science Foundation of China,No.82070869 and 82270914.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is a major health burden with an increasing global incidence.Unfortunately,the unavailability of knowledge underlying NAFLD pathogenesis inhibits effective preventive and therapeutic measures.AIM To explore the molecular mechanism of NAFLD.METHODS Whole genome sequencing(WGS)analysis was performed on liver tissues from patients with NAFLD(n=6)and patients with normal metabolic conditions(n=6)to identify the target genes.A NAFLD C57BL6/J mouse model induced by 16 wk of high-fat diet feeding and a hepatocyte-specific F-box only protein 2(FBXO2)overexpression mouse model were used for in vivo studies.Plasmid transfection,co-immunoprecipitation-based mass spectrometry assays,and ubiquitination in HepG2 cells and HEK293T cells were used for in vitro studies.RESULTS A total of 30982 genes were detected in WGS analysis,with 649 up-regulated and 178 down-regulated.Expression of FBXO2,an E3 ligase,was upregulated in the liver tissues of patients with NAFLD.Hepatocyte-specific FBXO2 overexpression facilitated NAFLD-associated phenotypes in mice.Overexpression of FBXO2 aggravated odium oleate(OA)-induced lipid accumulation in HepG2 cells,resulting in an abnormal expression of genes related to lipid metabolism,such as fatty acid synthase,peroxisome proliferator-activated receptor alpha,and so on.In contrast,knocking down FBXO2 in HepG2 cells significantly alleviated the OA-induced lipid accumulation and aberrant expression of lipid metabolism genes.The hydroxyl CoA dehydrogenase alpha subunit(HADHA),a protein involved in oxidative stress,was a target of FBXO2-mediated ubiquitination.FBXO2 directly bound to HADHA and facilitated its proteasomal degradation in HepG2 and HEK293T cells.Supplementation with HADHA alleviated lipid accumulation caused by FBXO2 overexpression in HepG2 cells.CONCLUSION FBXO2 exacerbates lipid accumulation by targeting HADHA and is a potential therapeutic target for NAFLD。
文摘As one of the largest gene families, F-box domain proteins have important roles in regulating various devel- opmental processes and stress responses. In this study, we have investigated a rice F-box domain gene, MAIF1. The MAIF1 protein is mainly localized in the plasma membrane and nucleus. MAIF1 expression is induced rapidly and strongly by abscisic acid （ABA） and abiotic stresses. MAIF1 expression is also induced in root tips by sucrose, independent of its hy- drolytic hexose products, glucose and fructose, and the plant hormones auxin and cytokinin. Overexpression of MAIF1 reduces rice ABA sensitivity and abiotic stress tolerance and promotes rice root growth. These results suggest that MAIF1 is involved in multiple signaling pathways in regulating root growth. Growth restraint in plants is an acclimatization strategy against abiotic stress, Our results also suggest that MAIF1 plays the negative role in response to abiotic stress possibly by regulating root growth.
基金supported by the project RTI2018-095946-B-I00 and PID2021-126956OB-I00 from MICIUby"Severo Ochoa Programme for Centres of Excellence in R&D"from the Agencia Estatal de Investigación of Spain(grants SEV-2016-0672 and CEX2020-000999-S to the CBGP)In the frame of this latter program,S.M.was supported with postdoctoral contracts.We also acknowledge the grant"Recualificación del profesorado universitario"from the Ministerio de Universidades to A.M.(UCO).
文摘Gibberellins(GAs)play important roles in multiple developmental processes and in plant response to the environment.Within the GA pathway,a central regulatory step relies on GA-dependent degradation of the DELLA transcriptional regulators.Nevertheless,the relevance of the stability of other key proteins in this pathway,such as SLY1 and SNE(the F-box proteins involved in DELLA degradation),remains unknown.Here,we take advantage of mutants in the HSP70-HSP90 organizing protein(HOP)co-chaperones and reveal that these proteins contribute to the accumulation of SNE in Arabidopsis.Indeed,HOP proteins,along with HSP90 and HSP70,interact in vivo with SNE,and SNE accumulation is significantly reduced in the hop mutants.Concomitantly,greater accumulation of the DELLA protein RGA is observed in these plants.In agreement with these molecular phenotypes,hop mutants show a hypersensitive response to the GA inhibitor paclobutrazol and display a partial response to the ectopic addition of GA when GA-regulated processes are assayed.These mutants also display different phenotypes associated with alterations in the GA pathway,such as reduced germination rate,delayed bolting,and reduced hypocotyl elongation in response to warm temperatures.Remarkably,ectopic overexpression of SNE reverts the delay in germination and the thermally dependent hypocotyl elongation defect of the hop1 hop2 hop3 mutant,revealing that SNE accumulation is the key aspect of the hop mutant phenotypes.Together,these data reveal a pivotal role for HOP in SNE accumulation and GA signaling.
文摘Ma et al recently reported in the World Journal of Diabetes that ferroptosis occurs in osteoblasts under high glucose conditions,reflecting diabetes pathology.This condition could be protected by the upregulation of the gene encoding polycytosine RNA-binding protein 1(PCBP1).Additionally,Ma et al used a lentivirus infection system to express PCBP1.As the authors’method of administration can be improved in terms of stability and cost,we propose delivering PCBP1 to treat type 2 diabetic osteoporosis by encapsulating it in protein nanoparticles.First,PCBP1 is small and druggable.Second,intravenous injection can help deliver PCBP1 across the mucosa while avoiding acid and enzyme-catalyzed degradation.Furthermore,incorporating PCBP1 into nanoparticles prevents its interaction with water or oxygen and protects PCBP1’s structure and activity.Notably,the safety of the protein materials and the industrialization techniques for large-scale production of protein nanoparticles must be comprehensively investigated before clinical application.
