自噬相关蛋白ATG5/BECLIN-1调控细胞自噬和凋亡的分子机理研究进展

摘要

ATG5和BECLIN-1(酵母 ATG6同源物)是自噬体形成过程中所必需的两种自噬相关蛋白质,它们除了促进自噬体的形成,还能诱导细胞凋亡的发生,被认为是调控细胞自噬和凋亡的分子开关蛋白.前期研究揭示 ATG5通过组成泛素化系统 ATG5-ATG12-ATG16L介导自噬体的形成,而BECLIN-1通过组成磷脂酰肌醇3-激酶(PtdIns3KC3)复合体诱导细胞自噬,现在认为 ATG5的氨基端截短分子 tATG5-N和BECLIN-1的羧基端截短分子 BECLIN-1-C 能诱导细胞凋亡.本研究对近年来 ATG5和 BECLIN-1调控细胞自噬和凋亡的研究进展作一综述,为研究 ATG5/BECLIN-1调控细胞自噬和凋亡的分子机理奠定基础.%ATG5 and BECLIN-1 belong to two kind of crucial autophagy-related proteins included the formation of autoph-agosomes,in addition to the promotion of autophagy,enhances susceptibility towards apoptotic stimuli,therefore,ATG5 and BECLIN-1 are considered to be a molecular link between autophagy and apoptosis.Preliminary data revealed that ATG5 media-ted the formation of autophagosomes by ATG5-ATG12-ATG16L ubiquitination system,while BECLIN-1 induces autophagy by phosphatidylino3-kinase (PtdIns3KC3)complex.But now it is believed that truncated ATG5(tATG5-N)and truncated BEC-LIN-1(BECLIN-1-C),an amino-terminal cleavage product of ATG5 and carboxyl-terminal cleavage product of BECLIN-1, could induce apoptosis.The research summarize the progress on ATG5 and BECLIN-1 regulated autophagy and apoptosis,so as to further reveal the molecular mechanism of they regulate autophagy and apoptosis.