BACKGROUND： Post-translational （PT） modification in cells regulates many intracellular events like signal transduction, transcription, cell cycle, protein quality control, apoptosis and cellular development. Ubiqui...BACKGROUND： Post-translational （PT） modification in cells regulates many intracellular events like signal transduction, transcription, cell cycle, protein quality control, apoptosis and cellular development. Ubiquitination is one of the PT modifications which ftmctions as a marker for degradation of target proteins by the proteasome and as a regulatory mechanism for several signalling pathways. The ubiquitination mechanism requires multiple enzymes, including El, E2, and E3 ligases. Among them, E3 ligases play a major role in recognizing target proteins and an essential feature of protein homeostatic mechanisms within the cell. Most of the ASB （ankyrin repeat SOCS box） proteins fimction as RING family of E3 ubiquitin ligases characterized by the presence of two conserved domains N-terminal ankyrin repeat and C-terminal SOCS box domain METHODS and RESULTS： Current studies have shown that some ASBs function as important regulators of several signalling pathways. This review gives an overview of ASB proteins on numerous cellular processes such as insulin signalling, spermatogenesis, myogenesis and in cellular development. Including various pathological situations, such as cancer, primary open-angle glaucoma, and inflammation, indicating that ASBs has important functions in both normal and pathological development CONCLUSIONS： This article provides a precise comprehensive focus on ASBs protein structure, its biological functions, and their pathological significance.展开更多
Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradatio...Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.展开更多
本试验采用单核苷酸多态性(single nucleotide polymorphism,SNP)直接测序法检测猪锚蛋白重复序列和SOCS盒蛋白基因4(ankyrin repeat and SOCS box containing protein 4,Asb4)与生长因子受体结合蛋白基因10(growth factor recep-tor-bo...本试验采用单核苷酸多态性(single nucleotide polymorphism,SNP)直接测序法检测猪锚蛋白重复序列和SOCS盒蛋白基因4(ankyrin repeat and SOCS box containing protein 4,Asb4)与生长因子受体结合蛋白基因10(growth factor recep-tor-bound protein 10,Grb10)在不同组织器官中的印迹状态。首先,克隆得到了1350bp的Asb4基因cDNA序列及1811bp的Grb10基因cDNA序列,然后进行了SNP直接测序法检测。结果发现,Asb4在1月龄仔猪所有检测组织器官中均为双等位基因表达,而Grb10在1月龄仔猪的舌、肾脏、胃、小肠和脑中为父源等位基因表达,在其他组织器官中为双等位基因表达。实时定量PCR结果表明,Grb10在10种组织器官中的表达量存在显著性差异(P<0.05),其中在肺脏组织中的表达量最高,在小肠和脑中表达量最低。上述结果表明,Grb10可能是猪父源表达的印迹基因,而Asb4则属于猪非印迹基因。展开更多
文摘BACKGROUND： Post-translational （PT） modification in cells regulates many intracellular events like signal transduction, transcription, cell cycle, protein quality control, apoptosis and cellular development. Ubiquitination is one of the PT modifications which ftmctions as a marker for degradation of target proteins by the proteasome and as a regulatory mechanism for several signalling pathways. The ubiquitination mechanism requires multiple enzymes, including El, E2, and E3 ligases. Among them, E3 ligases play a major role in recognizing target proteins and an essential feature of protein homeostatic mechanisms within the cell. Most of the ASB （ankyrin repeat SOCS box） proteins fimction as RING family of E3 ubiquitin ligases characterized by the presence of two conserved domains N-terminal ankyrin repeat and C-terminal SOCS box domain METHODS and RESULTS： Current studies have shown that some ASBs function as important regulators of several signalling pathways. This review gives an overview of ASB proteins on numerous cellular processes such as insulin signalling, spermatogenesis, myogenesis and in cellular development. Including various pathological situations, such as cancer, primary open-angle glaucoma, and inflammation, indicating that ASBs has important functions in both normal and pathological development CONCLUSIONS： This article provides a precise comprehensive focus on ASBs protein structure, its biological functions, and their pathological significance.
基金supported by the National Natural Science Foundation of China (No. 81472256, 81272638)the Guangdong Provincial Science and Technology Project (No. 2016A020215081, 2016A020217007)the National High Technology Research and Development Program of China (863 Program, No. 2012AA02A204)
文摘Background: Ankyrin repeat and SOCS box protein 3(ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer(CRC).Methods: We used next?generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real?time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony for?mation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.Results: We found that ASB3 gene was frequently mutated(5.3%) and down?regulated(70.4%) in CRC cases. Knock?down of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild?type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial?mesenchymal transition, which was characterized by the up?regulation of β?catenin and E?cadherin and the down?regulation of transcription factor 8, N?cadherin, and vimentin.Conclusion: ASB3 dysfunction resulted from gene mutations or down?regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.
文摘本试验采用单核苷酸多态性(single nucleotide polymorphism,SNP)直接测序法检测猪锚蛋白重复序列和SOCS盒蛋白基因4(ankyrin repeat and SOCS box containing protein 4,Asb4)与生长因子受体结合蛋白基因10(growth factor recep-tor-bound protein 10,Grb10)在不同组织器官中的印迹状态。首先,克隆得到了1350bp的Asb4基因cDNA序列及1811bp的Grb10基因cDNA序列,然后进行了SNP直接测序法检测。结果发现,Asb4在1月龄仔猪所有检测组织器官中均为双等位基因表达,而Grb10在1月龄仔猪的舌、肾脏、胃、小肠和脑中为父源等位基因表达,在其他组织器官中为双等位基因表达。实时定量PCR结果表明,Grb10在10种组织器官中的表达量存在显著性差异(P<0.05),其中在肺脏组织中的表达量最高,在小肠和脑中表达量最低。上述结果表明,Grb10可能是猪父源表达的印迹基因,而Asb4则属于猪非印迹基因。
