FAM105A通过caspase依赖性途径和Bcl-2家族诱导细胞凋亡

摘要

Apoptosis plays a crucial role in mediating normal cellular activities and development in multicellular organisms. Characterization and mechanistic elucidation of proteins involved in apoptosis are important for understanding this process. FAM 105 A is a newly identified pro-apoptotic gene,whose overexpression results in cell apoptosis. However,the mechanism underlying FAM105A-mediated apoptosis remains elusive. In this study.it was found that overexpression of FAM105A in HEK293T cells induced cleavage/ activation of caspase-3 and caspase-9, accompanied with cleavage/inactivation of the poly ADP-ribose polymerase (PARP). In addition, overexpression of FAM105A induced cytochrome c(Cyt c)release from mitochondria to the cytosol. Moreover,overexpression of FAM105A increased and decreased the levels of pro-apoptotic Bax and anti-apoptotic Bcl-2, respectively. These results suggest that FAM105A-mediated apoptosis requires the involvement of the caspase-dependent pathway and the Bcl-2 family.%在多细胞有机体中,细胞凋亡对调节正常细胞活动和发育起着关键作用.对参与细胞凋亡的蛋白的鉴定及其机制的阐明具有重要意义.FAM 105A是新发现的促凋亡基因,过表达会导致细胞凋亡.研究了FAM105A促进细胞凋亡的潜在机制,结果表明,在HEK293T细胞中过表达FAM105A会导致caspase-3和caspase-9的剪切/激活,同时伴随着多聚ADP-核糖聚合酶(poly ADP ribose polymerase,PARP)的切割/失活.此外,过表达FAM105A能诱导细胞色素c(Cyt c)从线粒体释放到胞质,促凋亡蛋白Bax的表达水平升高,而抗凋亡蛋白Bcl-2的表达水平下降.这些结果表明FAM105A诱导的细胞凋亡过程需要caspase依赖性途径和Bcl-2家族共同参与.