Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death
DC Field | Value | Language |
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dc.contributor.author | Kim, C. | - |
dc.contributor.author | Yun, N. | - |
dc.contributor.author | Lee, J. | - |
dc.contributor.author | Youdim, M. B. H. | - |
dc.contributor.author | Ju, C. | - |
dc.contributor.author | Kim, W-K | - |
dc.contributor.author | Han, P-L | - |
dc.contributor.author | Oh, Y. J. | - |
dc.date.accessioned | 2021-09-04T03:37:51Z | - |
dc.date.available | 2021-09-04T03:37:51Z | - |
dc.date.created | 2021-06-16 | - |
dc.date.issued | 2016-02 | - |
dc.identifier.issn | 1350-9047 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/89733 | - |
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.language.iso | en | - |
dc.publisher | NATURE PUBLISHING GROUP | - |
dc.subject | APOPTOSIS-INDUCING FACTOR | - |
dc.subject | CYCLIN-DEPENDENT KINASE-5 | - |
dc.subject | UBIQUITIN-LIGASE ACTIVITY | - |
dc.subject | HEAT-SHOCK PROTEINS | - |
dc.subject | CELL-DEATH | - |
dc.subject | NEURODEGENERATIVE DISEASES | - |
dc.subject | PARKINSONS-DISEASE | - |
dc.subject | E3 LIGASE | - |
dc.subject | HSP70-INTERACTING PROTEIN | - |
dc.subject | NEGATIVE REGULATION | - |
dc.title | Phosphorylation of CHIP at Ser20 by Cdk5 promotes tAIF-mediated neuronal death | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, W-K | - |
dc.identifier.doi | 10.1038/cdd.2015.103 | - |
dc.identifier.scopusid | 2-s2.0-84954078841 | - |
dc.identifier.wosid | 000368062200014 | - |
dc.identifier.bibliographicCitation | CELL DEATH AND DIFFERENTIATION, v.23, no.2, pp.333 - 346 | - |
dc.relation.isPartOf | CELL DEATH AND DIFFERENTIATION | - |
dc.citation.title | CELL DEATH AND DIFFERENTIATION | - |
dc.citation.volume | 23 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 333 | - |
dc.citation.endPage | 346 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.subject.keywordPlus | APOPTOSIS-INDUCING FACTOR | - |
dc.subject.keywordPlus | CYCLIN-DEPENDENT KINASE-5 | - |
dc.subject.keywordPlus | UBIQUITIN-LIGASE ACTIVITY | - |
dc.subject.keywordPlus | HEAT-SHOCK PROTEINS | - |
dc.subject.keywordPlus | CELL-DEATH | - |
dc.subject.keywordPlus | NEURODEGENERATIVE DISEASES | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | E3 LIGASE | - |
dc.subject.keywordPlus | HSP70-INTERACTING PROTEIN | - |
dc.subject.keywordPlus | NEGATIVE REGULATION | - |
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