Huang Xin, Qi Qiangqian, Hua Xuming, Li Xinyuan, Zhang Wenchuan, Sun Hui, Li Shiting, Wang Xiaoqiang, Li Bin
Department of Neurosurgery, 171 Hospital, Jiujiang, Jiangxi 33200, P.R. China.
Department of Neurosurgery, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Rep. 2014 Apr;31(4):1761-7. doi: 10.3892/or.2014.3015. Epub 2014 Feb 10.
Beclin 1 acts as a tumor suppressor and is an essential mediator of autophagy. Beclin 1 also interacts with Bcl-2 and can induce apoptosis by activating the mitochondrion permeabilizing function of proapoptotic multidomain proteins from the Bcl-2 family. Moreover, these Bcl-2 family members can activate autophagy by liberating Beclin 1 from its inhibition by Bcl-2/Bcl-XL at the level of the endoplasmic reticulum. We found that overexpression of Beclin 1 in U87 glioblastoma cells enhanced the capacity for cellular autophagy and induced apoptosis. Silencing of Beclin 1 decreased autophagic capacity but had little effect on apoptosis and cell proliferation. Beclin 1-Bcl-2 and Beclin 1-Bcl-xL complexes were detected by immunoprecipitation in cells that overexpressed Beclin 1. Furthermore, the levels of cytochrome c in the cytosol and the activity of caspases-3/-9 in the cytosol increased after overexpression of Beclin 1. Our results suggest that Beclin 1 induces apoptosis via binding to Bcl-2 and Bcl-xL, followed by the release of cytochrome c into the cytosol and activation of caspases-3/-9.
Beclin 1作为一种肿瘤抑制因子，是自噬的关键介导因子。Beclin 1还能与Bcl-2相互作用，并通过激活Bcl-2家族促凋亡多结构域蛋白的线粒体通透功能来诱导细胞凋亡。此外，这些Bcl-2家族成员可通过在内质网水平上使Beclin 1从其被Bcl-2/Bcl-XL的抑制中释放出来，从而激活自噬。我们发现，在U87胶质母细胞瘤细胞中过表达Beclin 1可增强细胞自噬能力并诱导细胞凋亡。沉默Beclin 1会降低自噬能力，但对细胞凋亡和细胞增殖影响不大。在过表达Beclin 1的细胞中，通过免疫沉淀检测到了Beclin 1-Bcl-2和Beclin 1-Bcl-xL复合物。此外，过表达Beclin 1后，细胞质中细胞色素c的水平以及细胞质中半胱天冬酶-3/-9的活性均有所增加。我们的结果表明，Beclin 1通过与Bcl-2和Bcl-xL结合来诱导细胞凋亡，随后细胞色素c释放到细胞质中并激活半胱天冬酶-3/-9。
