Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and b...Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.展开更多
It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular ...It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.展开更多
Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV p...Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.展开更多
The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named C...The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named CGI-55,or plasminogen activator inhibitor type-1-RNA binding protein-1,indicating that they might be paralog proteins,possibly with similar or redundant functions in human cells.Through the identification of their protein interactomes,both regulatory proteins have been functionally implicated in transcriptional regulation,mRNA metabolism,specifically RNA splicing,the regulation of mRNA stability,especially,in the context of the progesterone hormone response,and the DNA damage response.Both proteins also show a complex pattern of post-translational modifications,involving Ser/Thr phosphorylation,mainly through protein kinase C,arginine methylation and SUMOylation,suggesting that their functions and locations are highly regulated.Furthermore,they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies,upon stress,and nuclear splicing speckles.Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis.This review highlights important aspects of the structure,interactome,post-translational modifications,sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.展开更多
In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determin...In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determined to be in the nu-cleolus inside the nucleus by the following bio-informatics tools: Hum-PLoc, Euk-PLoc and Nuc-PLoc. Based on our results signal peptides with average of 22 base pairs in N-terminal were identified in human PrPs. This theoretical study demonstrates that PrP is post-translationally modified by: 1) attachment of two N-linked complex carbohydrate moieties (N181 and N197), 2) attachmet of glycosylphosphatidylinositol (GPI) at serine 230 and 3) formation of two di-sulfide bonds between “6–22” and “179–214” cysteines. Furthermore, ten protein kinase phosphorylation sites were predicted in human PrP. The above-noted phosphorylation was car-ried out by PKC and CK2. By using bioinfor-matics tools, we have shown that computation-ally human PrPs locate particularly into the nu-cleolus.展开更多
Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and...Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.展开更多
The formation of mature proteins requires complex post-translational modification and processing.Efficient posttranslational processing machinery is beneficial for the high-quality expression of proteins.To comprehens...The formation of mature proteins requires complex post-translational modification and processing.Efficient posttranslational processing machinery is beneficial for the high-quality expression of proteins.To comprehensively evaluate the role of post-translational mediating factors(PTMFs)in protein synthesis,two reporter strains expressing a homologous protein,Amy15A,and a heterologous protein,TaEG,were constructed in Penicillium oxalicum.Three PTMFs including a conserved basic leucine zipper transcription factor,HacA;an endoplasmic reticulum chaperone-binding protein,BipA;and a protein disulfide isomerase,PdiA,were individually overexpressed in the both reporter strains.The findings showed that overexpression of these PTMFs enhanced the enzymatic activity of both homologous and heterologous proteins.However,sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that,upon overexpression of the PTMFs,heterologous protein secretion remained stable or slightly increased,whereas that of homologous proteins remained unchanged or decreased.Neither the vegetative growth rate nor reporter transcription levels accounted for these variations in protein production or enzymatic activity.Conclusively,this study suggests that PTMFs play a positive role in protein expression and can be leveraged to optimize filamentous fungal chassis cells in the future.展开更多
Y box binding protein-1(YBX1)belongs to a DNA-and RNA-binding family of transcription factors,containing the highly conserved cold shock domain(CSD).YBX1 is involved in a number of cellular functions including transcr...Y box binding protein-1(YBX1)belongs to a DNA-and RNA-binding family of transcription factors,containing the highly conserved cold shock domain(CSD).YBX1 is involved in a number of cellular functions including transcription,translation,DNA damage repair etc.,and it is upregulated during times of environmental stress.YBX1 is localized in both the cytoplasm and the nucleus.There,its nuclear translocation is observed in a number of cancers and is associated with poor prognosis and disease progression.Additionally,YBX1 expression is upregulated in a variety of cancers,pointing towards its role as a potential oncogene.Under certain circumstances,YBX1 also promotes the expression of multidrug resistance 1(MDR1)gene,which is involved in the development of drug resistance.Thus,it is critical to understand the mechanism of YBX1 regulation and its downstream effects on promoting cancer development.A number of recent studies have highlighted the mechanisms of YBX1 regulation.Mass spectrometric analyses have reported several post-translational modifications that possibly play an important role in modulating YBX1 function.Phosphorylation is the most widely occurring post-translational modification in YBX1.In vivo analyses of sites like S102 and more recently,S165 illustrate the relationship of post-translational regulation of YBX1 in promoting cell proliferation and tumor growth.This review provides a comprehensive and up-to-date account of post-translational modifications identified in YBX1.This knowledge is a key in allowing us to better understand the mechanism of YBX1 regulation,which will aid in development of novel therapeutic strategies to target YBX1 in many types of cancer in the future.展开更多
Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Re...Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes,such as tumor-igenesis and metabolic diseases.To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms,we reviewed the current literature about Ksuc,mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools.We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical prac-tice.A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.展开更多
Post-translational modifications(PTMs)play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality.PTMs involve the covalent attachment of distinct chemical groups,such as suc...Post-translational modifications(PTMs)play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality.PTMs involve the covalent attachment of distinct chemical groups,such as succinyl,crotonyl,and lactyl,at specific protein sites,which alter protein structure,function,stability,and activity,ultimately influencing biological processes.Recently,metabolically derived short-chain acylation modifications(with acyl groups containing fewer than six carbon atoms)have been progressively identified,such as butyrylation,succinylation,crotonylation,and lactylation,differing from traditional acetylation in structure,physicochemical properties,function,and regulation.Aberrant short-chain acyl-PTMs are often associated with tumorigenesis.Research highlights that PTMs like succinylation and lactylation are essential in regulating tumor metabolism,drug resistance,and immune responses.This review elucidates the regulatory mechanisms of eight short-chain acyl-PTMs—butyrylation,succinylation,crotonylation,malonylation,glutarylation,2-hydroxyisobutyrylation,β-hydroxybutyrylation,and lactylation—that are involved in tumor initiation and progression.Their roles in controlling tumor genomic stability,gene transcription,protein stability,enzyme activity,and nuclear localization are summarized,demonstrating their impact on related biological processes such as tumor metabolism,multi-drug resistance,and immune evasion.Additionally,the review provides an overview of current drug research targeting enzymes that regulate PTMs,offering critical insights to advance therapeutic strategies for cancer treatment.展开更多
The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Co...The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Compared to the Spike protein,which is the primary target for currently available vaccines or antibodies,knowledge about other virion structural components is incomplete.Using high-resolution mass spectrometry,we report a comprehensive post-translational modification(PTM)analysis of nucleocapsid phosphoprotein(NCP),the most abundant structural component of the SARS-CoV-2 virion.In addition to phosphoryl groups,we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs,including N-glycans and ubiquitin.Based on newly identified PTMs,refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs.These data can facilitate the design of novel vaccines or therapeutics targeting NCP,as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.展开更多
Proteins containing an SPX domain are involved in numerous aspects of phosphate homeostasis and the response to phosphate deficiency.SPX4 is known to bind to the transcription factor PHR2 in the presenee of inositol p...Proteins containing an SPX domain are involved in numerous aspects of phosphate homeostasis and the response to phosphate deficiency.SPX4 is known to bind to the transcription factor PHR2 in the presenee of inositol polyphosphate,affecting its ability to activate the expression of phosphate-starvation-induced (PSI) genes.Plants have evolved mechanisms to coordinate the uptake and utilization of phosphate and nitrate.Two recent works (Hu et al.,2019;Ruan et al.,2019) have identified different E3 ubiquitin ligases that mediate the degradation of SPX4 under either phosphate-deficient conditions or nitrate-replete conditions.These studies highlight the potential of SPX proteins,E3 ubiquitin ligases,and inositol polyphosphate to regulate distinet nutrient signaling pathways in a coordinated fashion.展开更多
Heavy metal ions in shellfish products are harmful to human health,and their removal with low nutrient loss remains challenging.Herein,a new type of mesoporous silica(SBA15),modified internally with ammonium pyrrolidi...Heavy metal ions in shellfish products are harmful to human health,and their removal with low nutrient loss remains challenging.Herein,a new type of mesoporous silica(SBA15),modified internally with ammonium pyrrolidine dithiocarbamate(APDC)and externally with alkyl-diol groups,which was named as Diol-APDC-SBA15,was successfully developed and characterized by powder X-ray diffraction patterns,nitrogen adsorption,and Fourier transform infrared spectroscopy.The solutions with lead,chromium,cadmium,and copper were used to investigate the adsorption capacity of Diol-APDC-SBA15.Diol-APDC-SBA15 was adopted to remove heavy metals from cooking liquids of clams(Ruditapes philippinarum),hydrolysate liquids of oysters(Ostrea gigas Thunberg),and polysaccharide solution from the cooking liquid of R.philippinarum.The efficiencies of removing heavy metal ions and the loss rates of proteins and polysaccharides were examined.The results showed that the adsorption capacities of Diol-APDCSBA15 for Pb,Cr,Cd,and Cu in standard heavy-metal solutions were 161.4,166.1,29.6,and 60.2mgg^(−1),respectively.The removal efficiency of Diol-APDC-SBA15 for Pb in the three shellfish processing liquids ranged from 60.5%to 99.6%.The Cr removal efficiency was above 99.9%in the oyster hydrolysate liquid.Meanwhile,the percentages of polysaccharide loss were 5.5%and 3.7%in the cooking liquid of clam and polysaccharide solution,respectively,and the protein loss was 1.2%in the oyster hydrolysate liquid.Therefore,the Diol-APDC-SBA15 material exhibits a great potential application in the removal of heavy metals from shellfish processing liquids with low losses of proteins and polysaccharides.展开更多
With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute...With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute to flavor and texture.We systematically constructed the relationship between abalone protein,processing,and proteomics.This paper reviews the nutritional properties of abalone proteins and evaluates the effects of different thermal processing techniques,non-thermal processing,and freezing on abalone proteins.In addition,we synthesize published abalone proteomics studies and the use of proteomics technology to better elucidate the quality changes of abalone and its products,and as a technical basis for the study of blue food marker proteins.It is important direction to clearly explain the protein composition and meat quality mechanism of abalone in the processing and storage by proteomic.During various types of thermal processing,non-thermal processing,and freezing of abalone,the various chemical forces between protein molecules are disrupted,which in turn leads to different degrees of denaturation,aggregation,and gelation,which may have an impact on the organoleptic properties,bioavailability,and digestibility of abalone muscle.Proteomics is used in abalone biology studies to understand developmental biology,physiology,disease,stress,and species identification and can also be a powerful tool to characterize processing methods on abalone quality properties.展开更多
High molecular weight glutenin subunits(HMW-GS),major components of seed storage proteins in wheat,have large effects on processing quality.GLU-1 genes encode HMW-GS and their expression is mainly controlled at the tr...High molecular weight glutenin subunits(HMW-GS),major components of seed storage proteins in wheat,have large effects on processing quality.GLU-1 genes encode HMW-GS and their expression is mainly controlled at the transcriptional level by interactions between cis-regulatory elements and transcription factors.We previously identified an Aux/IAA transcription factor TaIAA10-6D that bound to a conserved cis-regulatory module CCRM1-1,the most essential conserved cis-regulatory module in GLU-1.Here,we confirmed the binding of TaIAA10-6D to CCRM1-1 using yeast one hybrid and dualluciferase reporter assays.The enhanced expression of TaIAA10-6D suppressed glutenin accumulation and increased gliadin content.Dynamic transcriptome analyses revealed that TaIAA10-6D overexpression down-regulated glutenin and gliadin genes during an early stage of grain filling,but up-regulated gliadin genes during a late stage probably by endoplasmic reticulum stress,accounting for its effect on the tradeoff between glutenin and gliadin.Rheological property and processing quality assays showed that TaIAA10-6D overproduction reduced stabilization time and bread quality,but enhanced cookie quality.Overexpression of TaIAA10-6D also reduced plant height,leaf size,kernel number and grain yield.We identified two major haplotypes of TaIAA10-6D,Hap I and Hap II,and developed a breeding-friendly diagnostic marker.Hap I conferred higher expression of TaIAA10-6D and concomitantly reduced plant height and kernel number,but had little effect on grain yield,contributing to lodging resistance without yield penalty.Hap I was subjected to positive selection in breeding.The findings provide a useful gene for wheat improvement and broaden insights into the regulatory machinery underpinning auxin-mediated quality formation,plant morphogenesis and yield gain.展开更多
The profile of polypeptides separated by SDS-PAGE from seed of major crop species such as pea (Pisum sativum) is complex, resulting from cleavage (processing) of precursors expressed from multiple copies of genes enco...The profile of polypeptides separated by SDS-PAGE from seed of major crop species such as pea (Pisum sativum) is complex, resulting from cleavage (processing) of precursors expressed from multiple copies of genes encoding vicilin and legumin, the major storage globulins. Translation in vitro of mRNAs hybrid-selected from mid-maturation pea seed RNAs by denned vicilin and legumin cDNA clones provided precursor molecules that were cleaved in vitro by a cell-free protease extract obtained from similar stage seed; the derived polypep tides were of comparable sizes to those observed in vivo. The feasibility of transcribing mENA in vitro from a cDNA clone and cleavage in vitro of the derived translation products was established for a legumin clone, providing a method for determining polypeptide products of an expressed sequence. This approach will also be useful for characterising cleavage site requirements since modifications an readily be introduced at the DNA level.展开更多
Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether ...Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.展开更多
Proteolytic processing of the transmembrane amyloid precursor protein (APP) to aggregation-prone amyloid-β (Aβ) peptide underlies the development of Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China(32061143005,32170313,and 32100266)Shandong Provincial Natural Science Foundation(ZR2021QC022 and ZR2022QC059).
文摘Protein post-translational modifications(PTMs),such as ubiquitination,phosphorylation,and small ubiquitin-like modifier(SUMO)ylation,are crucial for regulating protein stability,activity,subcellular localization,and binding with cofactors.Such modifications remarkably increase the variety and complexity of proteomes,which are essential for regulating numerous cellular and physiological processes.The regulation of auxin signaling is finely tuned in time and space to guide various plant growth and development.Accumulating evidence indicates that PTMs play critical roles in auxin signaling regulations.Thus,a thorough and systematic review of the functions of PTMs in auxin signal transduction will improve our profound comprehension of the regulation mechanism of auxin signaling and auxin-mediated various processes.This review discusses the progress of protein ubiquitination,phosphorylation,histone acetylation and methylation,SUMOylation,and S-nitrosylation in the regulation of auxin signaling.
文摘It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.
基金Supported by Canadian Institutes of Health Research,Saskatchewan Health Research Foundation,and Natural Sciences and Engineering Research Council of Canada
文摘Replication of hepatitis C virus(HCV)depends on the interaction of viral proteins with various host cellular proteins and signalling pathways.Similar to cellular proteins,post-translational modifications(PTMs)of HCV proteins are essential for proper protein function and regulation,thus,directly affecting viral life cycle and the generation of infectious virus particles.Cleavage of the HCV polyprotein by cellular and viral proteases into more than 10 proteins represents an early protein modification step after translation of the HCV positivestranded RNA genome.The key modifications include the regulated intramembranous proteolytic cleavage of core protein,disulfide bond formation of core,glycosylation of HCV envelope proteins E1 and E2,methylation of nonstructural protein 3(NS3),biotinylation of NS4A,ubiquitination of NS5B and phosphorylation of core and NS5B.Other modifications like ubiquitination of core and palmitoylation of core and NS4B proteins have been reported as well.For some modifications such as phosphorylation of NS3 and NS5A and acetylation of NS3,we have limited understanding of their effects on HCV replication and pathogenesis while the impact of other modifications is far from clear.In this review,we summarize the available information on PTMs of HCV proteins and discuss their relevance to HCV replication and pathogenesis.
文摘The amyloid beta precursor protein (APP) and its pathogenic byproduct β-amyloid peptide (Aβ) play central roles in the pathogenesis of Alzheimer’s disease (AD). Reduction in
基金Supported by the “Conselho Nacional de Desenvolvimento Cientifico e Tecnológico”,Grant No.302534/2017-2the “Fundacao de Amparo a Pesquisa do Estado de Sao Paulo”(FAPESP,Grant 2014/21700-3,to JK)
文摘The 57 kDa antigen recognized by the Ki-1 antibody,is also known as intracellular hyaluronic acid binding protein 4 and shares 40.7%identity and 67.4%similarity with serpin mRNA binding protein 1,which is also named CGI-55,or plasminogen activator inhibitor type-1-RNA binding protein-1,indicating that they might be paralog proteins,possibly with similar or redundant functions in human cells.Through the identification of their protein interactomes,both regulatory proteins have been functionally implicated in transcriptional regulation,mRNA metabolism,specifically RNA splicing,the regulation of mRNA stability,especially,in the context of the progesterone hormone response,and the DNA damage response.Both proteins also show a complex pattern of post-translational modifications,involving Ser/Thr phosphorylation,mainly through protein kinase C,arginine methylation and SUMOylation,suggesting that their functions and locations are highly regulated.Furthermore,they show a highly dynamic cellular localization pattern with localizations in both the cytoplasm and nucleus as well as punctuated localizations in both granular cytoplasmic protein bodies,upon stress,and nuclear splicing speckles.Several reports in the literature show altered expressions of both regulatory proteins in a series of cancers as well as mutations in their genes that may contribute to tumorigenesis.This review highlights important aspects of the structure,interactome,post-translational modifications,sub-cellular localization and function of both regulatory proteins and further discusses their possible functions and their potential as tumor markers in different cancer settings.
文摘In the present work, computational analyses were applied to study the subcellular localiza-tion and posttranslational modifications of hu-man prion proteins (PrPs). The tentative location of prion protein was determined to be in the nu-cleolus inside the nucleus by the following bio-informatics tools: Hum-PLoc, Euk-PLoc and Nuc-PLoc. Based on our results signal peptides with average of 22 base pairs in N-terminal were identified in human PrPs. This theoretical study demonstrates that PrP is post-translationally modified by: 1) attachment of two N-linked complex carbohydrate moieties (N181 and N197), 2) attachmet of glycosylphosphatidylinositol (GPI) at serine 230 and 3) formation of two di-sulfide bonds between “6–22” and “179–214” cysteines. Furthermore, ten protein kinase phosphorylation sites were predicted in human PrP. The above-noted phosphorylation was car-ried out by PKC and CK2. By using bioinfor-matics tools, we have shown that computation-ally human PrPs locate particularly into the nu-cleolus.
文摘Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.
基金funded by the National Natural Science Foundation of China(31700019)the Natural Science Foundation of Hunan Province(2023JJ30395)the Natural Science Foundation of Changsha(kq2208169).
文摘The formation of mature proteins requires complex post-translational modification and processing.Efficient posttranslational processing machinery is beneficial for the high-quality expression of proteins.To comprehensively evaluate the role of post-translational mediating factors(PTMFs)in protein synthesis,two reporter strains expressing a homologous protein,Amy15A,and a heterologous protein,TaEG,were constructed in Penicillium oxalicum.Three PTMFs including a conserved basic leucine zipper transcription factor,HacA;an endoplasmic reticulum chaperone-binding protein,BipA;and a protein disulfide isomerase,PdiA,were individually overexpressed in the both reporter strains.The findings showed that overexpression of these PTMFs enhanced the enzymatic activity of both homologous and heterologous proteins.However,sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that,upon overexpression of the PTMFs,heterologous protein secretion remained stable or slightly increased,whereas that of homologous proteins remained unchanged or decreased.Neither the vegetative growth rate nor reporter transcription levels accounted for these variations in protein production or enzymatic activity.Conclusively,this study suggests that PTMFs play a positive role in protein expression and can be leveraged to optimize filamentous fungal chassis cells in the future.
基金This research is supported by grants 4186265(American Cancer Society)and 23-862-07 and 036433730102(Indiana University)to TL.
文摘Y box binding protein-1(YBX1)belongs to a DNA-and RNA-binding family of transcription factors,containing the highly conserved cold shock domain(CSD).YBX1 is involved in a number of cellular functions including transcription,translation,DNA damage repair etc.,and it is upregulated during times of environmental stress.YBX1 is localized in both the cytoplasm and the nucleus.There,its nuclear translocation is observed in a number of cancers and is associated with poor prognosis and disease progression.Additionally,YBX1 expression is upregulated in a variety of cancers,pointing towards its role as a potential oncogene.Under certain circumstances,YBX1 also promotes the expression of multidrug resistance 1(MDR1)gene,which is involved in the development of drug resistance.Thus,it is critical to understand the mechanism of YBX1 regulation and its downstream effects on promoting cancer development.A number of recent studies have highlighted the mechanisms of YBX1 regulation.Mass spectrometric analyses have reported several post-translational modifications that possibly play an important role in modulating YBX1 function.Phosphorylation is the most widely occurring post-translational modification in YBX1.In vivo analyses of sites like S102 and more recently,S165 illustrate the relationship of post-translational regulation of YBX1 in promoting cell proliferation and tumor growth.This review provides a comprehensive and up-to-date account of post-translational modifications identified in YBX1.This knowledge is a key in allowing us to better understand the mechanism of YBX1 regulation,which will aid in development of novel therapeutic strategies to target YBX1 in many types of cancer in the future.
基金supported by National Natural Science Foundation of China(No.82002172)Key Scientific Research Project Plan of Henan Province(No.20A180001)Innovation program of Henan university students(No.202110475033,20217003003).
文摘Lysine succinylation(Ksuc)is a novel protein post-translational modification(PTM)wherein a succinyl group modifies a lysine residue.Ksuc leads to significant chemical and struc-tural changes to the modified protein.Recent studies have shown that Ksuc might play an important role in organism physiology and some pathophysiological processes,such as tumor-igenesis and metabolic diseases.To provide an understanding of the molecular mechanism and functions of Ksuc in different organisms,we reviewed the current literature about Ksuc,mainly summarizing the research advances in eukaryotes and prokaryotes based on both traditional study methods and site prediction tools.We also discussed inhibitors or activators associated with Ksuc that may contribute to proteomic studies and could be useful in future clinical prac-tice.A deeper understanding of Ksuc may shed new light on life science at the protein level and could lead to novel therapeutic strategies for various diseases.
基金National Natural Science Foundation of China,Grant/Award Number:82272915Science and Technology Innovation Team Project of China Medical University,Grant/Award Number:CXTD2022007+3 种基金Beijing Xisike Clinical Oncology Research Foundation,Grant/Award Number:Y-Gilead2024-PT-0201China Postdoctoral Science Foundation,Grant/Award Numbers:2023MD734246,2025T180577Liaoning Province Natural Science Foundation Joint Fund,Grant/Award Number:2023-MSLH-396Doctoral Start-up Foundation of Liaoning Province,Grant/Award Number:2024-BS-066。
文摘Post-translational modifications(PTMs)play a pivotal role in epigenetic regulation and are key pathways for modulating protein functionality.PTMs involve the covalent attachment of distinct chemical groups,such as succinyl,crotonyl,and lactyl,at specific protein sites,which alter protein structure,function,stability,and activity,ultimately influencing biological processes.Recently,metabolically derived short-chain acylation modifications(with acyl groups containing fewer than six carbon atoms)have been progressively identified,such as butyrylation,succinylation,crotonylation,and lactylation,differing from traditional acetylation in structure,physicochemical properties,function,and regulation.Aberrant short-chain acyl-PTMs are often associated with tumorigenesis.Research highlights that PTMs like succinylation and lactylation are essential in regulating tumor metabolism,drug resistance,and immune responses.This review elucidates the regulatory mechanisms of eight short-chain acyl-PTMs—butyrylation,succinylation,crotonylation,malonylation,glutarylation,2-hydroxyisobutyrylation,β-hydroxybutyrylation,and lactylation—that are involved in tumor initiation and progression.Their roles in controlling tumor genomic stability,gene transcription,protein stability,enzyme activity,and nuclear localization are summarized,demonstrating their impact on related biological processes such as tumor metabolism,multi-drug resistance,and immune evasion.Additionally,the review provides an overview of current drug research targeting enzymes that regulate PTMs,offering critical insights to advance therapeutic strategies for cancer treatment.
基金supported by the National Natural Science Foundation of China(U20A20343)the National Key Research and Development Program(2017YFC1200204)+1 种基金Emergency Project of Zhejiang Provincial Department of Science and Technology(2020C03123-1)Fundamental Research Funds for the Central Universities(2018XZZX001-13).
文摘The devastating coronavirus disease 2019(COVID-19)pandemic has prompted worldwide efforts to study structural biological traits of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its viral components.Compared to the Spike protein,which is the primary target for currently available vaccines or antibodies,knowledge about other virion structural components is incomplete.Using high-resolution mass spectrometry,we report a comprehensive post-translational modification(PTM)analysis of nucleocapsid phosphoprotein(NCP),the most abundant structural component of the SARS-CoV-2 virion.In addition to phosphoryl groups,we show that the SARS-CoV-2 NCP is decorated with a variety of PTMs,including N-glycans and ubiquitin.Based on newly identified PTMs,refined protein structural models of SARS-CoV-2 NCP were proposed and potential immune recognition epitopes of NCP were aligned with PTMs.These data can facilitate the design of novel vaccines or therapeutics targeting NCP,as valuable alternatives to the current vaccination and treatment paradigm that is under threat of the ever-mutating SARS-CoV-2 Spike protein.
文摘Proteins containing an SPX domain are involved in numerous aspects of phosphate homeostasis and the response to phosphate deficiency.SPX4 is known to bind to the transcription factor PHR2 in the presenee of inositol polyphosphate,affecting its ability to activate the expression of phosphate-starvation-induced (PSI) genes.Plants have evolved mechanisms to coordinate the uptake and utilization of phosphate and nitrate.Two recent works (Hu et al.,2019;Ruan et al.,2019) have identified different E3 ubiquitin ligases that mediate the degradation of SPX4 under either phosphate-deficient conditions or nitrate-replete conditions.These studies highlight the potential of SPX proteins,E3 ubiquitin ligases,and inositol polyphosphate to regulate distinet nutrient signaling pathways in a coordinated fashion.
基金supported by the National Key R&D Program of China(No.2018YFD0901004)the National Natural Science Foundation of China(No.31601538)+2 种基金the Key Science and Technology Program of Liaoning Province(No.2020JH1/10200001)the Fundamental Research Foundation of Education Department of Liaoning Province(No.JL202008)the Science&Technology Innovation Foundation of Dalian(No.2019J12SN61).
文摘Heavy metal ions in shellfish products are harmful to human health,and their removal with low nutrient loss remains challenging.Herein,a new type of mesoporous silica(SBA15),modified internally with ammonium pyrrolidine dithiocarbamate(APDC)and externally with alkyl-diol groups,which was named as Diol-APDC-SBA15,was successfully developed and characterized by powder X-ray diffraction patterns,nitrogen adsorption,and Fourier transform infrared spectroscopy.The solutions with lead,chromium,cadmium,and copper were used to investigate the adsorption capacity of Diol-APDC-SBA15.Diol-APDC-SBA15 was adopted to remove heavy metals from cooking liquids of clams(Ruditapes philippinarum),hydrolysate liquids of oysters(Ostrea gigas Thunberg),and polysaccharide solution from the cooking liquid of R.philippinarum.The efficiencies of removing heavy metal ions and the loss rates of proteins and polysaccharides were examined.The results showed that the adsorption capacities of Diol-APDCSBA15 for Pb,Cr,Cd,and Cu in standard heavy-metal solutions were 161.4,166.1,29.6,and 60.2mgg^(−1),respectively.The removal efficiency of Diol-APDC-SBA15 for Pb in the three shellfish processing liquids ranged from 60.5%to 99.6%.The Cr removal efficiency was above 99.9%in the oyster hydrolysate liquid.Meanwhile,the percentages of polysaccharide loss were 5.5%and 3.7%in the cooking liquid of clam and polysaccharide solution,respectively,and the protein loss was 1.2%in the oyster hydrolysate liquid.Therefore,the Diol-APDC-SBA15 material exhibits a great potential application in the removal of heavy metals from shellfish processing liquids with low losses of proteins and polysaccharides.
基金supported by the Cross-disciplinary Integration Project of Fujian Agriculture and Forestry University(71202103C)Science and Technology Projects of Fuzhou Ocean Research Institute(2022F16).
文摘With the increasing per capita demand for animal protein,there is a growing interest in the abundant abalone protein resources.Abalone proteins are known for their nutritional and functional properties that contribute to flavor and texture.We systematically constructed the relationship between abalone protein,processing,and proteomics.This paper reviews the nutritional properties of abalone proteins and evaluates the effects of different thermal processing techniques,non-thermal processing,and freezing on abalone proteins.In addition,we synthesize published abalone proteomics studies and the use of proteomics technology to better elucidate the quality changes of abalone and its products,and as a technical basis for the study of blue food marker proteins.It is important direction to clearly explain the protein composition and meat quality mechanism of abalone in the processing and storage by proteomic.During various types of thermal processing,non-thermal processing,and freezing of abalone,the various chemical forces between protein molecules are disrupted,which in turn leads to different degrees of denaturation,aggregation,and gelation,which may have an impact on the organoleptic properties,bioavailability,and digestibility of abalone muscle.Proteomics is used in abalone biology studies to understand developmental biology,physiology,disease,stress,and species identification and can also be a powerful tool to characterize processing methods on abalone quality properties.
基金supported by the STI 2030-Major Projects(2023ZD0406903)the National Natural and Science Foundation of China(32272182)+1 种基金the Postdoctoral Fellowship Program of CPSF(GZC20241955)the Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences(CAAS).
文摘High molecular weight glutenin subunits(HMW-GS),major components of seed storage proteins in wheat,have large effects on processing quality.GLU-1 genes encode HMW-GS and their expression is mainly controlled at the transcriptional level by interactions between cis-regulatory elements and transcription factors.We previously identified an Aux/IAA transcription factor TaIAA10-6D that bound to a conserved cis-regulatory module CCRM1-1,the most essential conserved cis-regulatory module in GLU-1.Here,we confirmed the binding of TaIAA10-6D to CCRM1-1 using yeast one hybrid and dualluciferase reporter assays.The enhanced expression of TaIAA10-6D suppressed glutenin accumulation and increased gliadin content.Dynamic transcriptome analyses revealed that TaIAA10-6D overexpression down-regulated glutenin and gliadin genes during an early stage of grain filling,but up-regulated gliadin genes during a late stage probably by endoplasmic reticulum stress,accounting for its effect on the tradeoff between glutenin and gliadin.Rheological property and processing quality assays showed that TaIAA10-6D overproduction reduced stabilization time and bread quality,but enhanced cookie quality.Overexpression of TaIAA10-6D also reduced plant height,leaf size,kernel number and grain yield.We identified two major haplotypes of TaIAA10-6D,Hap I and Hap II,and developed a breeding-friendly diagnostic marker.Hap I conferred higher expression of TaIAA10-6D and concomitantly reduced plant height and kernel number,but had little effect on grain yield,contributing to lodging resistance without yield penalty.Hap I was subjected to positive selection in breeding.The findings provide a useful gene for wheat improvement and broaden insights into the regulatory machinery underpinning auxin-mediated quality formation,plant morphogenesis and yield gain.
文摘The profile of polypeptides separated by SDS-PAGE from seed of major crop species such as pea (Pisum sativum) is complex, resulting from cleavage (processing) of precursors expressed from multiple copies of genes encoding vicilin and legumin, the major storage globulins. Translation in vitro of mRNAs hybrid-selected from mid-maturation pea seed RNAs by denned vicilin and legumin cDNA clones provided precursor molecules that were cleaved in vitro by a cell-free protease extract obtained from similar stage seed; the derived polypep tides were of comparable sizes to those observed in vivo. The feasibility of transcribing mENA in vitro from a cDNA clone and cleavage in vitro of the derived translation products was established for a legumin clone, providing a method for determining polypeptide products of an expressed sequence. This approach will also be useful for characterising cleavage site requirements since modifications an readily be introduced at the DNA level.
基金supported by the National Natural Science Foundation of China (32102605)the Agricultural Science and Technology Innovation Program under Grant (CAAS-ASTIP-2020IAR)the Earmarked Fund for CARS (CARS-44)。
文摘Food allergens are mainly naturally-occurring proteins with immunoglobulin E(IgE)-binding epitopes.Understanding the structural and immunogenic characteristics of allergenic proteins is essential in assessing whether and how food processing techniques reduce allergenicity.We here discuss the impacts of food processing technologies on the modification of physicochemical,structural,and immunogenic properties of allergenic proteins.Detection techniques for characterizing changes in these properties of food allergens are summarized.Food processing helps to reduce allergenicity by aggregating or denaturing proteins,which masks,modifies,or destroys antigenic epitopes,whereas,it cannot eliminate allergenicity completely,and sometimes even improves allergenicity by exposing new epitopes.Moreover,most food processing techniques have been tested on purified food allergens rather than food products due to potential interference of other food components.We provide guidance for further development of processing operations that can decrease the allergenicity of allergenic food proteins without negatively impacting the nutritional profile.
文摘Proteolytic processing of the transmembrane amyloid precursor protein (APP) to aggregation-prone amyloid-β (Aβ) peptide underlies the development of Alzheimer’s disease.
