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Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells
Autophagy is described to be involved in homeostasis, development and disease, both as a survival and a death process. Its involvement in cell death proceeds from interrelationships with the apoptotic pathway. We focused on survival autophagy and investigated its interplays with the apoptotic machin...
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Published in: | PloS one 2010-01, Vol.5 (1), p.e8755-e8755 |
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description | Autophagy is described to be involved in homeostasis, development and disease, both as a survival and a death process. Its involvement in cell death proceeds from interrelationships with the apoptotic pathway. We focused on survival autophagy and investigated its interplays with the apoptotic machinery. We found that while Mcl-1 remained ineffective, Bcl-2 and Bcl-xL were required for starved cells to display a fully functional autophagic pathway as shown by proteolysis activity and detection of autophagic vesicles. Such pro-autophagic functions of Bcl-2 and Bcl-xL were independent of Bax. However they appeared to operate through non redundant mechanisms as Bcl-xL wielded a tighter control than Bcl-2 over the regulation of autophagy: unlike Bcl-2, Bcl-xL and Atg7 manipulation yielded identical phenotypes suggesting they could be components of the same signalling pathway; Bcl-xL subcellular localisation was modified upon starvation, and importantly Bcl-xL acted independently of Beclin 1. Still an intact BH3-binding site was required for Bcl-xL to stimulate a fully functional autophagic pathway. This study highlights that, in addition to their well-established anti-death function during apoptosis, Bcl-2 and Bcl-xL have a broader role in cell survival. Should Bcl-2 and Bcl-xL stand at the cross-roads between pro-survival and pro-death autophagy, this study introduces the new concept that the regulation of autophagy by Bcl-2 and Bcl-xL is adjusted according to its survival or death outcome. |
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This study highlights that, in addition to their well-established anti-death function during apoptosis, Bcl-2 and Bcl-xL have a broader role in cell survival. Should Bcl-2 and Bcl-xL stand at the cross-roads between pro-survival and pro-death autophagy, this study introduces the new concept that the regulation of autophagy by Bcl-2 and Bcl-xL is adjusted according to its survival or death outcome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0008755</identifier><identifier>PMID: 20090905</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis ; Apoptosis Regulatory Proteins - physiology ; Autophagy ; Autophagy - physiology ; Bax protein ; Bcl-2 protein ; Bcl-x protein ; bcl-X Protein - physiology ; Beclin-1 ; Binding sites ; Biochemistry ; Biochemistry/Cell Signaling and Trafficking Structures ; Cell Biology/Cell Signaling ; Cell Biology/Cellular Death and Stress Responses ; Cell death ; Cell Line, Tumor ; Cell survival ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - physiopathology ; Development and progression ; Fibroblasts ; Homeostasis ; Humans ; Kinases ; Machinery and equipment ; Mcl-1 protein ; Membrane Proteins - physiology ; Mortality ; Phagocytosis ; Proteins ; Proteolysis ; Proto-Oncogene Proteins c-bcl-2 - physiology ; Signal transduction ; Signaling ; Starvation ; Survival</subject><ispartof>PloS one, 2010-01, Vol.5 (1), p.e8755-e8755</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Priault et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Priault et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-9ca0225c06c28811050bab4fac92d5cef6860f4ebd75b5145c4c183bd29a39043</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1289252097/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1289252097?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20090905$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Linden, Rafael</contributor><creatorcontrib>Priault, Muriel</creatorcontrib><creatorcontrib>Hue, Erika</creatorcontrib><creatorcontrib>Marhuenda, Fanny</creatorcontrib><creatorcontrib>Pilet, Paul</creatorcontrib><creatorcontrib>Oliver, Lisa</creatorcontrib><creatorcontrib>Vallette, François M</creatorcontrib><title>Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Autophagy is described to be involved in homeostasis, development and disease, both as a survival and a death process. 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subjects | Apoptosis Apoptosis Regulatory Proteins - physiology Autophagy Autophagy - physiology Bax protein Bcl-2 protein Bcl-x protein bcl-X Protein - physiology Beclin-1 Binding sites Biochemistry Biochemistry/Cell Signaling and Trafficking Structures Cell Biology/Cell Signaling Cell Biology/Cellular Death and Stress Responses Cell death Cell Line, Tumor Cell survival Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - physiopathology Development and progression Fibroblasts Homeostasis Humans Kinases Machinery and equipment Mcl-1 protein Membrane Proteins - physiology Mortality Phagocytosis Proteins Proteolysis Proto-Oncogene Proteins c-bcl-2 - physiology Signal transduction Signaling Starvation Survival |
title | Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells |
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