Bcl-2/Beclin-1复合体在自噬中的调节作用

The Function of Bcl-2/Beclin-1 Complex in Autophagy Regulation

自噬(autophagy)是一种进化保守的溶酶体依赖性分解代谢途径,是细胞维持自稳态的重要机制之一,并参与多种疾病的发生.Beclin-1作为自噬体成核的关键分子之一,是1个调节自噬的关键靶点.Beclin-1有1个BH3结构域,Bcl-2、Bcl-XL等可以通过这个BH3结构域与Beclin-1结合而影响其活性.抗凋亡Bcl-2家族蛋白和Beclin-1的表达水平、磷酸化、分子的亚细胞定位以及BH3-only蛋白等,均可调节Beclin-1蛋白和Bcl-2家族蛋白结合水平,进而调控自噬的发生,并可能对细胞最终走向自噬还是凋亡起着关键作用.

Autophagy is an evolutionarily conserved lysosome-dependent catabolic mechanism to maintain cell homeostasis. The defect of autophagy was lined to the pathogenesis of many diseases. Beclin-1 is a key factor in the regulation of macroautophagy for its function to recruit key autophagy proteins in the forms of Beclin-1 containing core complex with Vps34, and VpslS. As a BH3-only Bel-2 family protein, Beclin-1 is regulated by Bcl-2 family proteins through its BH3 domain. The expression levels, phosphorylation, subcellular localizaon of Beelin-1 and other Bcl-2 family anti-apoptotic proteins, as well as other BH3-only proteins were known to regulate the Beclin-1 functions. Thus, Beelin-1 could be serving as a switching factor to determine whether the cells undergo autophagy or apoptosis.