Hand,foot and mouth disease(HFMD),mainly caused by enterovirus 71(EV71),has frequently occurred in the Asia-Pacific region,posing a significant threat to the health of infants and young children.Therefore,research on ...Hand,foot and mouth disease(HFMD),mainly caused by enterovirus 71(EV71),has frequently occurred in the Asia-Pacific region,posing a significant threat to the health of infants and young children.Therefore,research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important.The 3D polymerase,as the most critical RNA-dependent RNA polymerase(RdRp)for EV71 replication,is widely targeted to inhibit EV71 infection.In this study,we identified a novel host protein,AIMP2,capable of binding to 3D polymerase and inhibiting EV71 infection.Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2,which mediates the polyubiquitination and degradation of 3D polymerase.Furthermore,the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes.Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection,revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.展开更多
SMURF2(smad ubiquitination regulatory factor 2)属于HECT(homologous to E6AP C terminus)家族E3泛素连接酶,有研究报道SMURF2在不同类型癌症中发挥促癌或抑癌作用.本研究探讨了SMURF2在前列腺(癌)细胞中调节STAT1(signal transducer...SMURF2(smad ubiquitination regulatory factor 2)属于HECT(homologous to E6AP C terminus)家族E3泛素连接酶,有研究报道SMURF2在不同类型癌症中发挥促癌或抑癌作用.本研究探讨了SMURF2在前列腺(癌)细胞中调节STAT1(signal transducers and activators of transcription 1)蛋白的分子机制.首先通过数据库分析SMURF2在正常组织与肿瘤组织间的表达差异,然后选取前列腺正常细胞和多种前列腺癌细胞为实验材料,通过RT-PCR,Western blotting实验检测SMURF2在前列腺(癌)细胞中的表达水平,发现相对于前列腺正常细胞,SMURF2在前列腺癌细胞中表达更高.再通过Co-IP,免疫荧光和泛素化检测实验观察SMURF2对STAT1蛋白泛素化水平的影响,发现SMURF2可以增加STAT1蛋白的泛素化水平,并进一步促进前列腺癌细胞发生EMT(epithelial mesenchymal transformation).展开更多
基金supported by National Natural Science Foundation of China(32188101 and 81971976).
文摘Hand,foot and mouth disease(HFMD),mainly caused by enterovirus 71(EV71),has frequently occurred in the Asia-Pacific region,posing a significant threat to the health of infants and young children.Therefore,research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important.The 3D polymerase,as the most critical RNA-dependent RNA polymerase(RdRp)for EV71 replication,is widely targeted to inhibit EV71 infection.In this study,we identified a novel host protein,AIMP2,capable of binding to 3D polymerase and inhibiting EV71 infection.Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2,which mediates the polyubiquitination and degradation of 3D polymerase.Furthermore,the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes.Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection,revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies.
文摘SMURF2(smad ubiquitination regulatory factor 2)属于HECT(homologous to E6AP C terminus)家族E3泛素连接酶,有研究报道SMURF2在不同类型癌症中发挥促癌或抑癌作用.本研究探讨了SMURF2在前列腺(癌)细胞中调节STAT1(signal transducers and activators of transcription 1)蛋白的分子机制.首先通过数据库分析SMURF2在正常组织与肿瘤组织间的表达差异,然后选取前列腺正常细胞和多种前列腺癌细胞为实验材料,通过RT-PCR,Western blotting实验检测SMURF2在前列腺(癌)细胞中的表达水平,发现相对于前列腺正常细胞,SMURF2在前列腺癌细胞中表达更高.再通过Co-IP,免疫荧光和泛素化检测实验观察SMURF2对STAT1蛋白泛素化水平的影响,发现SMURF2可以增加STAT1蛋白的泛素化水平,并进一步促进前列腺癌细胞发生EMT(epithelial mesenchymal transformation).
文摘目的观察不同浓度高糖刺激后大鼠肾小球系膜细胞胞内Smad泛素调节因子2(Smurf2)的表达,探讨泛素化降解在糖尿病肾病中的作用。方法将体外培养的大鼠肾系膜细胞分别设正常对照组(葡萄糖浓度5.6 mmol/L)、20 mmol/L高糖组、30 mmol/L高糖组、甘露醇组。分别用real ti me quantitative PCR法和细胞免疫荧光染色法及激光共聚焦显微镜检测各组细胞Smurf2的mRNA和蛋白的表达。结果(1)正常对照组系膜细胞Smurf2的mRNA和蛋白表达较弱。(2)高糖组Smurf2的mRNA和蛋白表达较正常对照组增强(P<0.05),呈浓度依赖性。结论高糖可诱导肾系膜细胞Smurf2表达增强。提示泛素-蛋白酶体途径可能参与了糖尿病肾病的病理进程。