An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins
An insight into the mechanistic role of Beclin 1 and its inhibition by prosurvival Bcl-2 family proteins
复制标题
DOI：
10.4161/auto.5846
复制
发表时间：
2008-05-16
期刊：
影响因子：
13.3
通讯作者：
Oh, Byung-Ha
中科院分区：
文献类型：
--
作者：
Ku, Bonsu;Woo, Jae-Sung;Oh, Byung-Ha
由Beclin 1、PI(3)KC3和UVRAG组成的多蛋白复合物促进自噬体的形成，而这种活性被一系列抗凋亡的Bcl-2家族成员抑制。最近，我们发现小鼠γ -疱疹病毒68的病毒Bcl-2（称为m11）与Beclin - 1结合的亲和力明显高于与Beclin - 1弱相互作用的细胞Bcl-2或Bcl-X-L。(1)此外，结合亲和力与抑制细胞自噬体形成的效力直接相关。在这里，我们提供了额外的数据，表明Beclin I形成一个大的同质寡聚物，这种寡聚被M11的结合部分破坏。寡聚的Beclin 1被认为是一个平台，可以使许多相关蛋白分子协同作用，包括Bif-1，由于其BAR结构域，Bif-1可以直接参与膜上的自噬体生物发生。
A multiprotein complex composed of Beclin 1, PI(3)KC3 and UVRAG promotes autophagosome formation, while this activity is suppressed by a cohort of antiapoptotic Bcl-2 family members. Recently, we showed that a viral Bcl-2 of murine gamma-herpesvirus 68, known as M 11, binds to Beclin 1 with markedly high affinity in comparison with cellular Bcl-2 or Bcl-X-L that interacts with Beclin 1 weakly.(1) Furthermore, the binding affinity directly correlated with the potency of inhibition of autophagosome formation in cells. Herein, we present additional data showing that Beclin I forms a large homo-oligomer, and this oligornerization is partly disrupted by the binding of M11. Oligomerized Beclin 1 is proposed to serve as a platform enabling a concerted action of many molecules of the associating proteins, including Bif-1 that could be directly involved in autophagosome biogenesis on membranes owing to its BAR domain.