Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
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DOI：
10.1016/j.cell.2005.07.002
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发表时间：
2005-09-23
期刊：
影响因子：
64.5
通讯作者：
Levine, B
中科院分区：
文献类型：
--
作者：
Pattingre, S;Tassa, A;Levine, B
细胞凋亡和自噬都是受到严格调控的生物学过程，在组织稳态、发育和疾病中发挥核心作用。抗凋亡蛋白Bcl-2与进化上保守的自噬蛋白Beclin 1相互作用。然而，很少有人知道这种相互作用的功能意义。在这里，我们表明，野生型Bcl-2抗凋亡蛋白，但不是Beclin 1结合缺陷的Bcl-2突变体，抑制Beclin 1依赖的自噬在酵母和哺乳动物细胞和心脏Bcl-2转基因表达抑制小鼠心肌自噬。此外，不能与Bcl-2结合的Beclin 1突变体比野生型Beclin 1诱导更多的自噬，并且与野生型Beclin 1不同，促进细胞死亡。因此，Bcl-2不仅作为抗凋亡蛋白发挥作用，而且通过其与Beclin 1的抑制性相互作用作为抗自噬蛋白发挥作用。Bcl-2的这种抗自噬功能可能有助于将自噬维持在与细胞存活相容的水平，而不是细胞死亡。
Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. The antiapoptotic protein, Bcl-2, interacts with the evolutionarily conserved autophagy protein, Beclin 1. However, little is known about the functional significance of this interaction. Here, we show that wild-type Bcl-2 antiapoptotic proteins, but not Beclin 1 binding defective mutants of Bcl-2, inhibit Beclin 1-dependent autophagy in yeast and mammalian cells and that cardiac Bcl-2 transgenic expression inhibits autophagy in mouse heart muscle. Furthermore, Beclin 1 mutants that cannot bind to Bcl-2 induce more autophagy than wild-type Beclin 1 and, unlike wild-type Beclin 1, promote cell death. Thus, Bcl-2 not only functions as an antiapoptotic protein, but also as an antiautophagy protein via its inhibitory interaction with Beclin 1. This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death.