UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),U...UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.展开更多
Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating h...Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating hormonal homeostasis.In the ubiquitination cascade,ubiquitin-conjugating enzymes(UBCs)function as ubiquitin carriers to determine linkage specificity of ubiquitin chains.In rice(Oryza sativa),39 UBC genes are identified,but only one gene OsUBC12 has been functionally studied to promote seed germination under low-temperatures in japonica rice.To elucidate the role of UBCs in seed germination,we generated CRISPR-Cas9 mutants for 23 UBC genes and overexpressed 20 members in rice.Among them,seven UBC genes(OsUBC4/6/7/12/25/27/48)were found to regulate seed germination,with OsUBC27 and OsUBC48 acting through the ABA pathway.Exogenous ABA inhibitors restored the germination rate of osubc27^(CR).RT-qPCR analysis revealed that the ABA synthesis genes OsNCED1-5 were significantly upregulated in the mutants.Further differential ubiquitination proteomics in knockout mutants and wild-type plants showed that OsUBC27 regulates ABA homeostasis by modulating ubiquitination of the ABA-degrading protein OsABA8ox1,thereby balancing seed dormancy and germination.Sequence analysis identified distinct haplotypes of the seven OsUBCs that showed differential distribution between japonica and indica subspecies.Our study provides valuable molecular targets for developing rice varieties resistant to seed vivipary.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that u...BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that ubiquitinconjugating enzyme E2T(UBE2T)serves as a promising prognostic factor in human cancers,although the molecular mechanism of UBE2T in HCC remains unclear.AIM To investigate the clinical relevance and role of UBE2T in HCC development.METHODS UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed.A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells.qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells.Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay,respectively.Cell cycle distribution and apoptosis were determined by flow cytometry.The genes regulated by UBE2T were profiled by microarray assay.RESULTS UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues.High expression of UBE2T predicted a poor overall survival in HCC patients.In vitro,lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells.In vivo,the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing.The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown.Furthermore,apoptosis was increased by UBE2T knockdown.At the molecular level,numerous genes were dysregulated after UBE2T silencing,including IL-1B,FOSL1,PTGS2,and BMP6.CONCLUSION UBE2T plays an important role in cell cycle progression,apoptosis,and HCC development.展开更多
BACKGROUND Liver cancer ranks the third cause of cancer-related death worldwide.The most common type of liver cancer is hepatocellular carcinoma(HCC).The survival time for HCC patients is very limited by years due to ...BACKGROUND Liver cancer ranks the third cause of cancer-related death worldwide.The most common type of liver cancer is hepatocellular carcinoma(HCC).The survival time for HCC patients is very limited by years due to the lack of efficient treatment,failure of early diagnosis,and poor prognosis.Ubiquitination plays an essential role in the biochemical processes of a variety of cellular functions.AIM To investigate three ubiquitination-associated genes in HCC.METHODS Herein,the expression levels of ubiquitin-conjugating enzymes 2(UBE2)including UBE2C,UBE2T,and UBE2S in tumor samples of HCC patients and nontumor controls at the Cancer Genome Atlas(TCGA)database,was comprehensively analyzed.The relationship of UBE2 gene expression level with cancer stage,prognostic outcome,and TP53 mutant status was studied.RESULTS Our results showed that UBE2C,UBE2T,and UBE2S genes were overexpressed in HCC samples compared to non-tumor tissues.Dependent on the cancer progression stage,three UBE2 genes showed higher expression in tumor tissues at all four stages compared to non-tumor control samples.Furthermore,a significantly higher expression of these genes was found in stage 2 and stage 3 cancers compared to stage 1 cancer.Additionally,overexpression of those genes was negatively associated with prognostic outcome and overall survival time.Patients with TP53 mutation showed a higher expression level of three UBE2 genes,indicating an association between UBE2 expression with p53 function.CONCLUSION In summary,this study shed light on the potential roles of UBE2C,UBE2T,UBE2S on diagnostic and prognostic biomarkers for HCC.Moreover,based on our findings,it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms.展开更多
Ubiquitin-proteasome pathway (UPP) is a significant way of protein degradation and modification in eukaryotic cell and involved in a complex series of intracellular processes. As a key component in UPP,?ubiquitin-conj...Ubiquitin-proteasome pathway (UPP) is a significant way of protein degradation and modification in eukaryotic cell and involved in a complex series of intracellular processes. As a key component in UPP,?ubiquitin-conjugating enzyme (E2) plays an extremely important role in ubiquitin (Ub) transferring and substrate specific recognition. Abundant evidences have proved that UPP is involved in cells immune reaction caused by pathogens and the attendance of E2 has a significant effect on host cells and pathogen. This article presents an overview of the current research on E2s that is involved in immune response caused by viruses and bacteria.展开更多
UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the t...UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22_12_1 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.展开更多
Objective:To study the regulatory effect of ubiquitin-conjugating enzyme 2C (UBE2C) on the proliferation and invasion of neuroblastoma.Methods: SH-SY5Y neuroblastoma cell lines were cultured and randomly divided into ...Objective:To study the regulatory effect of ubiquitin-conjugating enzyme 2C (UBE2C) on the proliferation and invasion of neuroblastoma.Methods: SH-SY5Y neuroblastoma cell lines were cultured and randomly divided into UBE2C-siRNA group and NC-siRNA group that were transfected with UBE2C siRNA and NC siRNA respectively. 24 h after siRNA transfection, the RNA in the cells was extracted, and fluorescence quantitative PCR reaction was used to detect the mRNA expression of pro-proliferation genes YB-1, CyclinD1, CDK4, Aurora-A and Ki-67, anti-proliferation genes LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 as well as invasion genes KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9.Results: YB-1, CyclinD1, CDK4, Aurora-A, Ki-67, KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9 mRNA expression in UBE2C-siRNA group of cells were significantly lower than those in NC-siRNA group whereas LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 mRNA expression were significantly higher than those in NC-siRNA group.Conclusions: Inhibition of the UBE2C gene can regulate the expression of proliferation and invasion genes in neuroblastoma to hinder cell proliferation and invasion.展开更多
Objective: To study the correlation of KLF4 and UBE2C expression levels in neuroblastoma with cell adhesion and migration. Methods: A total of 56 children who were diagnosed with neuroblastoma in the Central Hospital ...Objective: To study the correlation of KLF4 and UBE2C expression levels in neuroblastoma with cell adhesion and migration. Methods: A total of 56 children who were diagnosed with neuroblastoma in the Central Hospital of Enshi Autonomous Prefecture between May 2014 and February 2017 were selected as the NB group of the study, and the lesion tissue was collected;38 children who were treated in the Central Hospital of Enshi Autonomous Prefecture due to serious hydronephrosis during the same period were selected as the control group of the study, and the normal adrenal gland tissue was collected. The mRNA expression and protein expression of KLF4 and UBE2C as well as the protein expression of cell adhesion molecules and migration molecules in clinical tissue samples were determined. Results: The mRNA expression and protein expression of KLF4 in neuroblastoma tissue of NB group were greatly lower than those of control group whereas the mRNA expression and protein expression of UBE2C were greatly higher than those of control group;PDLIM1, AMF, GPx1, L1CAM, Nrg1, RANK, RANKL, Inβ1, MTA1 and MMP9 protein expression in neuroblastoma tissue of NB group were greatly higher than those of control group, negatively correlated with the protein expression KLF4, and positively correlated with the protein expression of UBE2C. Conclusion: The low expression of KLF4 and the high expression of UBE2C in neuroblastoma can promote the adhesion and migration of tumor cells.展开更多
The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2...The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2D2 gene.Here,we report a lamprey(La UBE2D2)gene which contained 441-bp open reading frame(ORF)encoding 147 amino acids with a typical UBC domain.Real-time PCR assay showed that the highest expression of the protein in adult lamprey was in the leukocytes,the lowest expression was in the skin,kidney and liver.The high conservation in amino acid sequence of the La UBE2D2protein with the UBE2D2s from Homo sapiens,Danio rerio,Oreochromis niloticus and Takifugu rubripes,implied that it had similar function with UBE2D2proteins from other species.展开更多
Background:Ubiquitin-conjugating enzyme E2C(UBE2C)has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes.This study aimed to investigate the specific molecula...Background:Ubiquitin-conjugating enzyme E2C(UBE2C)has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes.This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer(BC)proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.Then differentially expressed genes(DEGs)were identified using Venn diagram analysis.By using DEGs,we conducted the following analyses including Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein-protein interaction(PPI),and survival analysis,and then validated the function of the hub geneUBE2C using quantitative reverse transcription-polymerase chain reaction(RT-qPCR),cell counting kit-8(CCK-8)assay,transwell assay,and Western blot assay.Results:In total,151 DEGs were identified from the GEO and TCGA databases.The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division,lipid droplet,and organic acid-binding.KEGG analysis showed that the peroxisome proliferators-activated receptor(PPAR)signaling pathway,regulation of lipolysis in adipocytes,and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category.The top three hub genes that resulted from the PPI network wereFOXM1,UBE2C,andCDKN3.The results of survival analysis showed a close relationship between UBE2C and BC.The results of CCK-8 and transwell assays suggested that the proliferation and invasion ofUBE2C knockdown cells were significantly inhibited(P<0.050).The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10(p-PTEN)was obviously increased(P<0.050),whereas the levels of phosphorylated protein kinase B(p-AKT),phosphorylated mammalian target of rapamycin(p-mTOR),and hypoxia-inducible factor-1 alpha(HIF-1α)were dramatically decreased(P<0.050)in theUBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.展开更多
Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitinati...Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitination may also play important roles in plant response to the phytohormone abscisic acid （ABA）. Many components of the ubiquitination pathway, such as ubiquitin-conjugating enzyme E2, ubiquitin ligase E3 and components of the proteasome, have been identified or predicted to be essential in ABA biosynthesis, catabolism and signaling. In addition, the ubiquitination-related pathway, sumoylation, is also involved in ABA signaling. We summarize in this report recent developments to elucidate their roles in the ABA-related pathway.展开更多
基金Supported by Special Projects in Key Areas for Guangdong Provincial Colleges and Universities (No.2021ZDZX2009)Guangzhou Medical University Discipline Construction Funds (Basic Medicine)(No.JCXKJS2022A05)。
文摘UBE2O is a distinctive ubiquitin-conjugating enzyme characterized by its large size(1292 residues)and dual E2/E3 enzymatic activities,enabling diverse ubiquitylation types.Unlike typical E2 enzymes(150~200 residues),UBE2O’s multifunctionality allows it to regulate substrate degradation,subcellular localization,and functional modulation.Emerging studies highlight its critical roles in protein quality control,erythroid differentiation,metabolic regulation,and maintenance of circadian rhythm.Dysregulation of UBE2O is implicated in various diseases,including cancers,neurodegenerative disorders,and metabolic diseases.This review extensively discusses the unique structural features,diverse biological functions,and pathological roles of UBE2O,as well as its therapeutic potential for associated diseases.
基金supported by the Zhejiang Provincial Natural Science Foundation,China(ZCLMS25C1302)the Central Public-interest Scientific Institution Basal Research Fund(CPSIBRF-CNRRI-202408)the Agricultural Science and Technology Innovation Program(ASTIP)
文摘Rice seed germination marks the start of cultivation and influences subsequent seedling growth,and is affected by hormones and environmental factors.Ubiquitination plays a critical role in this process by regulating hormonal homeostasis.In the ubiquitination cascade,ubiquitin-conjugating enzymes(UBCs)function as ubiquitin carriers to determine linkage specificity of ubiquitin chains.In rice(Oryza sativa),39 UBC genes are identified,but only one gene OsUBC12 has been functionally studied to promote seed germination under low-temperatures in japonica rice.To elucidate the role of UBCs in seed germination,we generated CRISPR-Cas9 mutants for 23 UBC genes and overexpressed 20 members in rice.Among them,seven UBC genes(OsUBC4/6/7/12/25/27/48)were found to regulate seed germination,with OsUBC27 and OsUBC48 acting through the ABA pathway.Exogenous ABA inhibitors restored the germination rate of osubc27^(CR).RT-qPCR analysis revealed that the ABA synthesis genes OsNCED1-5 were significantly upregulated in the mutants.Further differential ubiquitination proteomics in knockout mutants and wild-type plants showed that OsUBC27 regulates ABA homeostasis by modulating ubiquitination of the ABA-degrading protein OsABA8ox1,thereby balancing seed dormancy and germination.Sequence analysis identified distinct haplotypes of the seven OsUBCs that showed differential distribution between japonica and indica subspecies.Our study provides valuable molecular targets for developing rice varieties resistant to seed vivipary.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is now the most common primary liver malignancy worldwide,and multiple risk factors attribute to the occurrence and development of HCC.Recently,increasing studies suggest that ubiquitinconjugating enzyme E2T(UBE2T)serves as a promising prognostic factor in human cancers,although the molecular mechanism of UBE2T in HCC remains unclear.AIM To investigate the clinical relevance and role of UBE2T in HCC development.METHODS UBE2T expression in HCC tissues from the TCGA database and its association with patient survival were analyzed.A lentivirus-mediated strategy was used to knock down UBE2T in HCC cells.qRT-PCR and Western blot assays were performed to check the effect of UBE2T silencing in HCC cells.Cell growth in vitro and in vivo was analyzed by multiparametric high-content screening and the xenograft tumorigenicity assay,respectively.Cell cycle distribution and apoptosis were determined by flow cytometry.The genes regulated by UBE2T were profiled by microarray assay.RESULTS UBE2T was overexpressed in HCC tissues compared with paired and non-paired normal tissues.High expression of UBE2T predicted a poor overall survival in HCC patients.In vitro,lentivirus-mediated UBE2T knockdown significantly reduced the viability of both SMMC-7721 and BEL-7404 cells.In vivo,the xenograft tumorigenesis of SMMC-7721 cells was largely attenuated by UBE2T silencing.The cell cycle was arrested at G1/S phase in SMMC-7721 and BEL-7404 cells with UBE2T knockdown.Furthermore,apoptosis was increased by UBE2T knockdown.At the molecular level,numerous genes were dysregulated after UBE2T silencing,including IL-1B,FOSL1,PTGS2,and BMP6.CONCLUSION UBE2T plays an important role in cell cycle progression,apoptosis,and HCC development.
文摘BACKGROUND Liver cancer ranks the third cause of cancer-related death worldwide.The most common type of liver cancer is hepatocellular carcinoma(HCC).The survival time for HCC patients is very limited by years due to the lack of efficient treatment,failure of early diagnosis,and poor prognosis.Ubiquitination plays an essential role in the biochemical processes of a variety of cellular functions.AIM To investigate three ubiquitination-associated genes in HCC.METHODS Herein,the expression levels of ubiquitin-conjugating enzymes 2(UBE2)including UBE2C,UBE2T,and UBE2S in tumor samples of HCC patients and nontumor controls at the Cancer Genome Atlas(TCGA)database,was comprehensively analyzed.The relationship of UBE2 gene expression level with cancer stage,prognostic outcome,and TP53 mutant status was studied.RESULTS Our results showed that UBE2C,UBE2T,and UBE2S genes were overexpressed in HCC samples compared to non-tumor tissues.Dependent on the cancer progression stage,three UBE2 genes showed higher expression in tumor tissues at all four stages compared to non-tumor control samples.Furthermore,a significantly higher expression of these genes was found in stage 2 and stage 3 cancers compared to stage 1 cancer.Additionally,overexpression of those genes was negatively associated with prognostic outcome and overall survival time.Patients with TP53 mutation showed a higher expression level of three UBE2 genes,indicating an association between UBE2 expression with p53 function.CONCLUSION In summary,this study shed light on the potential roles of UBE2C,UBE2T,UBE2S on diagnostic and prognostic biomarkers for HCC.Moreover,based on our findings,it is appealing to further explore the correlation of those genes with TP53 mutation in HCC and the related mechanisms.
文摘Ubiquitin-proteasome pathway (UPP) is a significant way of protein degradation and modification in eukaryotic cell and involved in a complex series of intracellular processes. As a key component in UPP,?ubiquitin-conjugating enzyme (E2) plays an extremely important role in ubiquitin (Ub) transferring and substrate specific recognition. Abundant evidences have proved that UPP is involved in cells immune reaction caused by pathogens and the attendance of E2 has a significant effect on host cells and pathogen. This article presents an overview of the current research on E2s that is involved in immune response caused by viruses and bacteria.
基金supported by the National Natural Science Foundation of China(grants 21372078,81302697 and 81230090)the National S&T Major Project of China(grant 2013ZX09507004)+1 种基金the Shanghai Committee of Science and Technology(grant 14431902400)the Fundamental Research Funds for the Central Universities
文摘UbcH5c belongs to the ubiquitin-conjugating enzyme family and plays an important role in catalyzing ubiquitination during TNF-α–triggered NF-κB activation. Therefore, UbcH5c is a potent therapeutic target for the treatment of inflammatory and autoimmune diseases induced by aberrant activation of NF-κB. In this study, we established a stable expression system for recombinant UbcH5c and solved the crystal structure of UbcH5c belonging to space group P22_12_1 with one molecule in the asymmetric unit. This study provides the basis for further study of UbcH5c including the design of UbcH5c inhibitors.
文摘Objective:To study the regulatory effect of ubiquitin-conjugating enzyme 2C (UBE2C) on the proliferation and invasion of neuroblastoma.Methods: SH-SY5Y neuroblastoma cell lines were cultured and randomly divided into UBE2C-siRNA group and NC-siRNA group that were transfected with UBE2C siRNA and NC siRNA respectively. 24 h after siRNA transfection, the RNA in the cells was extracted, and fluorescence quantitative PCR reaction was used to detect the mRNA expression of pro-proliferation genes YB-1, CyclinD1, CDK4, Aurora-A and Ki-67, anti-proliferation genes LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 as well as invasion genes KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9.Results: YB-1, CyclinD1, CDK4, Aurora-A, Ki-67, KLF4, RIPK3, HIF-1α, Integrinβ1 and MMP9 mRNA expression in UBE2C-siRNA group of cells were significantly lower than those in NC-siRNA group whereas LC3, Beclin1, GRP78, IRE1α, PERK and ATF6 mRNA expression were significantly higher than those in NC-siRNA group.Conclusions: Inhibition of the UBE2C gene can regulate the expression of proliferation and invasion genes in neuroblastoma to hinder cell proliferation and invasion.
文摘Objective: To study the correlation of KLF4 and UBE2C expression levels in neuroblastoma with cell adhesion and migration. Methods: A total of 56 children who were diagnosed with neuroblastoma in the Central Hospital of Enshi Autonomous Prefecture between May 2014 and February 2017 were selected as the NB group of the study, and the lesion tissue was collected;38 children who were treated in the Central Hospital of Enshi Autonomous Prefecture due to serious hydronephrosis during the same period were selected as the control group of the study, and the normal adrenal gland tissue was collected. The mRNA expression and protein expression of KLF4 and UBE2C as well as the protein expression of cell adhesion molecules and migration molecules in clinical tissue samples were determined. Results: The mRNA expression and protein expression of KLF4 in neuroblastoma tissue of NB group were greatly lower than those of control group whereas the mRNA expression and protein expression of UBE2C were greatly higher than those of control group;PDLIM1, AMF, GPx1, L1CAM, Nrg1, RANK, RANKL, Inβ1, MTA1 and MMP9 protein expression in neuroblastoma tissue of NB group were greatly higher than those of control group, negatively correlated with the protein expression KLF4, and positively correlated with the protein expression of UBE2C. Conclusion: The low expression of KLF4 and the high expression of UBE2C in neuroblastoma can promote the adhesion and migration of tumor cells.
文摘The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2D2 gene.Here,we report a lamprey(La UBE2D2)gene which contained 441-bp open reading frame(ORF)encoding 147 amino acids with a typical UBC domain.Real-time PCR assay showed that the highest expression of the protein in adult lamprey was in the leukocytes,the lowest expression was in the skin,kidney and liver.The high conservation in amino acid sequence of the La UBE2D2protein with the UBE2D2s from Homo sapiens,Danio rerio,Oreochromis niloticus and Takifugu rubripes,implied that it had similar function with UBE2D2proteins from other species.
基金supported by a grant from the National Natural Science Foundation of China(No.82060520)。
文摘Background:Ubiquitin-conjugating enzyme E2C(UBE2C)has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes.This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer(BC)proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA)database.Then differentially expressed genes(DEGs)were identified using Venn diagram analysis.By using DEGs,we conducted the following analyses including Gene ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),protein-protein interaction(PPI),and survival analysis,and then validated the function of the hub geneUBE2C using quantitative reverse transcription-polymerase chain reaction(RT-qPCR),cell counting kit-8(CCK-8)assay,transwell assay,and Western blot assay.Results:In total,151 DEGs were identified from the GEO and TCGA databases.The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division,lipid droplet,and organic acid-binding.KEGG analysis showed that the peroxisome proliferators-activated receptor(PPAR)signaling pathway,regulation of lipolysis in adipocytes,and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category.The top three hub genes that resulted from the PPI network wereFOXM1,UBE2C,andCDKN3.The results of survival analysis showed a close relationship between UBE2C and BC.The results of CCK-8 and transwell assays suggested that the proliferation and invasion ofUBE2C knockdown cells were significantly inhibited(P<0.050).The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10(p-PTEN)was obviously increased(P<0.050),whereas the levels of phosphorylated protein kinase B(p-AKT),phosphorylated mammalian target of rapamycin(p-mTOR),and hypoxia-inducible factor-1 alpha(HIF-1α)were dramatically decreased(P<0.050)in theUBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.
基金Supported by the Ministry of Science and Technology of China （863- 2002AA224111）, the State Key Development Program of Basic Research of China （973-2003CB114304）, the National Natural Science Foundation of China （30325030 and 30530400） and the Knowledge Innovation Project of the Chinese Academy of Sciences. Publication of this paper is supported by the National Natural Science Foundation of China （30624808） and Science Publication Foundation of the Chinese Academy of Sciences.
文摘Ubiquitination is emerging as a tight regulatory mechanism that is necessary for all aspects of development and survival of all eukaryotes. Recent genomic and genetic analysis in Arabidopsis suggests that ubiquitination may also play important roles in plant response to the phytohormone abscisic acid （ABA）. Many components of the ubiquitination pathway, such as ubiquitin-conjugating enzyme E2, ubiquitin ligase E3 and components of the proteasome, have been identified or predicted to be essential in ABA biosynthesis, catabolism and signaling. In addition, the ubiquitination-related pathway, sumoylation, is also involved in ABA signaling. We summarize in this report recent developments to elucidate their roles in the ABA-related pathway.
