Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death.

Show simple item record Kerr, LE en Birse-Archbold, JL en Short, DM en McGregor, Ailsa en Heron, I en Macdonald, DC en Thompson, J en Carlson, G en Kelly, JS en McCulloch, J en Sharkey, J en 2012-03-06T00:51:21Z en 2006 en
dc.identifier.issn 0950-9232 en
dc.identifier.uri en
dc.description.abstract The proapoptotic B-cell lymphoma-2family protein Bax is a key regulatory point in the intrinsic apoptotic pathway. However, the factors controlling the process of Bax activation and translocation to mitochondria have yet to be fully identified and characterized. We performed affinity chromatography using peptides corresponding to the mitochondrial-targeting region of Bax, which is normally sequestered within the inactive structure. The molecular chaperone nucleophosmin was identified as a novel Bax-binding protein by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Reciprocal co-immunoprecipitation and proximity assays confirmed the Bax-nucleophosmin protein–protein interaction and verified that nucleophosmin only bound to activated conformationally altered Bax. Confocal microscopy in a cell-based apoptosis model, demonstrated that nucleophosmin translocation from nucleolus to cytosol preceded Bax movement. Specific knockdown of nucleophosmin expression using RNAi attenuated apoptosis as measured by mitochondrial cytochrome c release and activation of the caspase cascade. In a mouse model of ischaemic stroke, subcellular fractionation studies verified that nucleophosmin translocation occurred within 3 h, at a time before Bax translocation but after Bax conformational changes have occurred. Thus, we have elucidated a novel molecular mechanism whereby Bax becomes activated and translocates to the mitochondria to orchestrate mitochondrial dysfunction and apoptotic cell death, which opens new avenues for therapeutic intervention. en
dc.description.uri;jsessionid=CB5DB93ADA8D952107ABF918CEC486A2 en
dc.publisher Nature Publishing Group en
dc.relation.ispartofseries Oncogene en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from en
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dc.title Nucleophosmin is a novel Bax chaperone that regulates apoptotic cell death. en
dc.type Journal Article en
dc.identifier.doi 10.1038/sj.onc.1210044 en
pubs.issue 18 en
pubs.volume 26 en
dc.rights.holder Copyright: Nature Publishing Group en
dc.identifier.pmid 17072349 en
dc.rights.accessrights en
pubs.subtype Article en
pubs.elements-id 66995 en
pubs.record-created-at-source-date 2010-09-01 en
pubs.dimensions-id 17072349 en

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