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dc.contributor.author Wang, Qinhong en_US
dc.date.accessioned 2011-06-21T17:32:17Z
dc.date.available 2011-06-21T17:32:17Z
dc.date.issued 2010 en_US
dc.identifier.citation Wang,Qinhong;Sun,Shi-Yong;Khuri,Fadlo;Curran,Walter J.;Deng,Xingming. 2010. Mono- or Double-Site Phosphorylation Distinctly Regulates the Proapoptotic Function of Bax. Plos One 5(10): e13393-e13393. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://hdl.handle.net/10161/4578
dc.description.abstract Bax is the major multidomain proapoptotic molecule that is required for apoptosis. It has been reported that phosphorylation of Bax at serine(S) 163 or S184 activates or inactivates its proapoptotic function, respectively. To uncover the mechanism(s) by which phosphorylation regulates the proapoptotic function of Bax, a series of serine (S)-> alanine/glutamate (A/E) Bax mutants, including S163A, S184A, S163E, S184E, S163E/S184A (EA), S163A/S184E (AE), S163A/S184A (AA) and S163E/S184E (EE), were created to abrogate or mimic, respectively, either single or double-site phosphorylation. The compound Bax mutants (i.e. EA and AE) can flesh out the functional contribution of individual phosphorylation site(s). WT and each of these Bax mutants were overexpressed in Bax(-/-) MEF or lung cancer H157 cells and the proapoptotic activities were compared. Intriguingly, expression of any of Bax mutants containing the mutation S -> A at S184 (i.e. S184A, EA or AA) represents more potent proapoptotic activity as compared to WT Bax in association with increased 6A7 epitope conformational change, mitochondrial localization/insertion and prolonged half-life. In contrast, all Bax mutants containing the mutation S -> E at S184 (i.e. S184E, AE or EE) have a mobility-shift and fail to insert into mitochondrial membranes with decreased protein stability and less apoptotic activity. Unexpectedly, mutation either S -> A or S -> E at S163 site does not significantly affect the proapoptotic activity of Bax. These findings indicate that S184 but not S163 is the major phosphorylation site for functional regulation of Bax's activity. Therefore, manipulation of the phosphorylation status of Bax at S184 may represent a novel strategy for cancer treatment. en_US
dc.language.iso en_US en_US
dc.publisher PUBLIC LIBRARY SCIENCE en_US
dc.relation.isversionof doi:10.1371/journal.pone.0013393 en_US
dc.subject mitochondrial-membrane permeabilization en_US
dc.subject cytochrome-c release en_US
dc.subject bcl-x-l en_US
dc.subject cell-death en_US
dc.subject conformational-change en_US
dc.subject bh3 domains en_US
dc.subject apoptosis en_US
dc.subject protein en_US
dc.subject activation en_US
dc.subject survival en_US
dc.subject biology en_US
dc.subject multidisciplinary sciences en_US
dc.title Mono- or Double-Site Phosphorylation Distinctly Regulates the Proapoptotic Function of Bax en_US
dc.title.alternative en_US
dc.description.version Version of Record en_US
duke.date.pubdate 2010-10-14 en_US
duke.description.endpage e13393 en_US
duke.description.issue 10 en_US
duke.description.startpage e13393 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US

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