| The autophagy protein atg12 associates with antiapoptotic bcl-2 family members to promote mitochondrial apoptosis. | |
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MedLine Citation:
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PMID: 22152474 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Autophagy and apoptosis constitute important determinants of cell fate and engage in a complex interplay in both physiological and pathological settings. The molecular basis of this crosstalk is poorly understood and relies, in part, on "dual-function" proteins that operate in both processes. Here, we identify the essential autophagy protein Atg12 as a positive mediator of mitochondrial apoptosis and show that Atg12 directly regulates the apoptotic pathway by binding and inactivating prosurvival Bcl-2 family members, including Bcl-2 and Mcl-1. The binding occurs independently of Atg5 or Atg3 and requires a unique BH3-like motif in Atg12, characterized by interaction studies and computational docking. In apoptotic cells, knockdown of Atg12 inhibited Bax activation and cytochrome c release, while ectopic expression of Atg12 antagonized the antiapoptotic activity of Mcl-1. The interaction between Atg12 and Bcl-2 family members may thus constitute an important point of convergence between autophagy and apoptosis in response to specific signals. |
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Authors:
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Assaf D Rubinstein; Miriam Eisenstein; Yaara Ber; Shani Bialik; Adi Kimchi |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Molecular cell Volume: 44 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 698-709 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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