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dc.contributor.author한평림-
dc.date.accessioned2016-08-27T04:08:50Z-
dc.date.available2016-08-27T04:08:50Z-
dc.date.issued2016-
dc.identifier.issn1350-9047-
dc.identifier.issn1476-5403-
dc.identifier.otherOAK-15342-
dc.identifier.urihttp://dspace.ewha.ac.kr/handle/2015.oak/217424-
dc.description.abstractCyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/ threonine kinase and its dysregulation is implicated in neurodegenerative diseases. Likewise, C-terminus of Hsc70-interacting protein (CHIP) is linked to neurological disorders, serving as an E3 ubiquitin ligase for targeting damaged or toxic proteins for proteasomal degradation. Here, we demonstrate that CHIP is a novel substrate for Cdk5. Cdk5 phosphorylates CHIP at Ser20 via direct binding to a highly charged domain of CHIP. Co-immunoprecipitation and ubiquitination assays reveal that Cdk5-mediated phosphorylation disrupts the interaction between CHIP and truncated apoptosis-inducing factor (tAIF) without affecting CHIP's E3 ligase activity, resulting in the inhibition of CHIP-mediated degradation of tAIF. Lentiviral transduction assay shows that knockdown of Cdk5 or overexpression of CHIPS20A, but not CHIPWT, attenuates tAIF-mediated neuronal cell death induced by hydrogen peroxide. Thus, we conclude that Cdk5-mediated phosphorylation of CHIP negatively regulates its neuroprotective function, thereby contributing to neuronal cell death progression following neurotoxic stimuli.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.titlePhosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death-
dc.typeArticle-
dc.relation.issue2-
dc.relation.volume23-
dc.relation.indexSCIE-
dc.relation.indexSCOPUS-
dc.relation.startpage333-
dc.relation.lastpage346-
dc.relation.journaltitleCELL DEATH AND DIFFERENTIATION-
dc.identifier.doi10.1038/cdd.2015.103-
dc.identifier.wosidWOS:000368062200014-
dc.identifier.scopusid2-s2.0-84954078841-
dc.author.googleKim, C.-
dc.author.googleYun, N.-
dc.author.googleLee, J.-
dc.author.googleYoudim, M. B. H.-
dc.author.googleJu, C.-
dc.author.googleKim, W-K-
dc.author.googleHan, P-L-
dc.author.googleOh, Y. J.-
dc.contributor.scopusid한평림(7201947605)-
dc.date.modifydate20170601143155-
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일반대학원 > 뇌·인지과학과 > Journal papers
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