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Bcl-xL and E1B-19K Proteins Inhibit p53-induced Irreversible Growth Arrest and Senescence by Preventing Reactive Oxygen Species-dependent p38 Activation

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dc.contributor.authorJung, Mun-Su-
dc.contributor.authorJin, Dong-Hoon-
dc.contributor.authorChae, Hee-Don-
dc.contributor.authorKang, Seokwon-
dc.contributor.authorKim, Sun-Chang-
dc.contributor.authorBang, Yung-Jue-
dc.contributor.authorChoi, Tae-Saeng-
dc.contributor.authorChoi, Kyeong-sook-
dc.contributor.authorShin, Deug Y.-
dc.date.accessioned2021-01-31T11:04:31Z-
dc.date.available2021-01-31T11:04:31Z-
dc.date.issued2004-04-
dc.identifier.citationJournal of Biological Chemistry, Vol.279 No.17, pp.17765-17771-
dc.identifier.issn0021-9258-
dc.identifier.other119221-
dc.identifier.urihttps://hdl.handle.net/10371/173005-
dc.description.abstractIn this study, we describe novel functions of the antiapoptotic Bcl-2 family proteins. Bcl-x(L) and E1B-19K were found to inhibit p53-induced irreversible growth arrest and senescence, but not to inhibit transient growth arrest, implying that Bcl-x(L) and E1B-19K are specifically involved in senescence without participating in growth arrest. We provide several lines of evidences showing that the functions of Bcl-x(L) and E1B-19K to prevent generation of reactive oxygen species (ROS) are important to inhibit senescence induction. First, we found that that ROS are increased during p53-induced senescence. Moreover, Bcl-x(L) and E1B-19K inhibit this p53-induced ROS generation. Second, antioxidants prevent the induction of senescence and ROS by p53, but not the persistence of the senescence phenotype. Third, the anti-senescence functions of Bcl-x(L) and E1B-19K were suppressed by adding exogenous ROS. These results suggest that Bcl-x(L) and E1B-19K inhibit senescence induction by preventing ROS generation. Furthermore, p38 kinase was found to be activated during p53-induced senescence, but not in cells expressing Bcl-x(L) or E1B-19K, or in cells treated with anti-oxidants. Consistently, a chemical inhibitor of p38 kinase, SB203580, was found to inhibit p53-induced senescence, but only when treated before the cellular commitment to senescence, implying that p38 kinase is necessary for senescence induction. Therefore, Bcl-x(L) and E1B-19K inhibit p53-induced senescence by preventing ROS generation, which in turn leads to the activation of p38 kinase. These results also suggest that the oncogenic potential of Bcl-2 is due to its ability to inhibit senescence as well as apoptosis.-
dc.titleBcl-xL and E1B-19K Proteins Inhibit p53-induced Irreversible Growth Arrest and Senescence by Preventing Reactive Oxygen Species-dependent p38 Activation-
dc.typeArticle-
dc.contributor.AlternativeAuthor방영주-
dc.identifier.doi10.1074/jbc.M305015200-
dc.citation.journaltitleJournal of Biological Chemistry-
dc.identifier.scopusid2-s2.0-2342431845-
dc.citation.endpage17771-
dc.citation.number17-
dc.citation.startpage17765-
dc.citation.volume279-
dc.identifier.urlhttps://www.jbc.org/content/279/17/17765-
dc.identifier.rimsid119221-
dc.identifier.sci000220870400108-
dc.contributor.affiliatedAuthorBang, Yung-Jue-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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