Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.
Apoptosis and autophagy are both tightly regulated biological processes that play a central role in tissue homeostasis, development, and disease. The anti-apoptotic 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.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Animals, Apoptosis, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Endoplasmic Reticulum, Gene Expression Regulation, Hela Cells, Humans, Membrane Proteins, Mice, Mice, Transgenic, Mitochondria, Mutation, Myocytes, Cardiac, Proteins, Proto-Oncogene Proteins c-bcl-2, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Starvation
1-Phosphatidylinositol 3-Kinase, Animals, Apoptosis, Apoptosis Regulatory Proteins, Autophagy, Cell Line, Endoplasmic Reticulum, Gene Expression Regulation, Hela Cells, Humans, Membrane Proteins, Mice, Mice, Transgenic, Mitochondria, Mutation, Myocytes, Cardiac, Proteins, Proto-Oncogene Proteins c-bcl-2, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Starvation
Cell
Date: Sep. 23, 2005
PubMed ID: 16179260
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