Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 한평림 | - |
dc.date.accessioned | 2016-08-27T04:08:50Z | - |
dc.date.available | 2016-08-27T04:08:50Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.issn | 1476-5403 | - |
dc.identifier.other | OAK-15342 | - |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/217424 | - |
dc.description.abstract | Cyclin-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.language | English | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.title | Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death | - |
dc.type | Article | - |
dc.relation.issue | 2 | - |
dc.relation.volume | 23 | - |
dc.relation.index | SCI | - |
dc.relation.index | SCIE | - |
dc.relation.index | SCOPUS | - |
dc.relation.startpage | 333 | - |
dc.relation.lastpage | 346 | - |
dc.relation.journaltitle | CELL DEATH AND DIFFERENTIATION | - |
dc.identifier.doi | 10.1038/cdd.2015.103 | - |
dc.identifier.wosid | WOS:000368062200014 | - |
dc.identifier.scopusid | 2-s2.0-84954078841 | - |
dc.author.google | Kim, C. | - |
dc.author.google | Yun, N. | - |
dc.author.google | Lee, J. | - |
dc.author.google | Youdim, M. B. H. | - |
dc.author.google | Ju, C. | - |
dc.author.google | Kim, W-K | - |
dc.author.google | Han, P-L | - |
dc.author.google | Oh, Y. J. | - |
dc.contributor.scopusid | 한평림(7201947605) | - |
dc.date.modifydate | 20230901081001 | - |