File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Cyclin-dependent kinase 5 supports neuronal survival through phosphorylation of Bcl-2

TitleCyclin-dependent kinase 5 supports neuronal survival through phosphorylation of Bcl-2
Authors
KeywordsChemicals And Cas Registry Numbers: Protein Bcl 2, 219306-68-0
Serine, 56-45-1, 6898-95-9
Cyclin-Dependent Kinase 5, Ec 2.7.1.37
Neuroprotective Agents
Proto-Oncogene Proteins C-Bcl-2
Issue Date2008
PublisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.org
Citation
Journal Of Neuroscience, 2008, v. 28 n. 19, p. 4872-4877 How to Cite?
AbstractAccumulating evidence indicates that deregulation of cyclin-dependent kinase 5 (Cdk5) activity is associated with apoptosis in various neurodegenerative disease models. Interestingly, recent studies suggest that Cdk5 may also favor neuronal survival. Nonetheless, whether Cdk5 is directly required for neuronal survival during development remains enigmatic. In the current study, we established the pivotal role of Cdk5 in neuronal survival during development by demonstrating that reduction or absence of Cdk5 activity markedly exacerbated neuronal death in cultures and in vivo. Interestingly, the antiapoptotic protein Bcl-2 (B-cell lymphoma protein 2) was identified as a novel substrate of Cdk5. We found that Cdk5-mediated phosphorylation of Bcl-2 at Ser70 was required for the neuroprotective effect of Bcl-2. Intriguingly, inhibition of this phosphorylation conferred proapoptotic property to Bcl-2. Furthermore, overexpression of a Bcl-2 mutant lacking the Cdk5 phosphorylation site abolished the protective effect of Cdk5 re-expression in Cdk5-/- neurons, suggesting that Ser70 phosphorylation of Bcl-2 contributed to Cdk5-mediated neuronal survival. Our observations revealed that Cdk5-mediated Bcl-2 phosphorylation is pivotal for the antiapoptotic effect of Bcl-2 and contributes to the maintenance of neuronal survival by Cdk5. Our study has also identified Cdk5 as a regulator of Bcl-2 function in neuronal apoptosis. Copyright © 2008 Society for Neuroscience.
Persistent Identifierhttp://hdl.handle.net/10722/145816
ISSN
2015 Impact Factor: 5.924
2015 SCImago Journal Rankings: 5.105
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCheung, ZHen_HK
dc.contributor.authorGong, Ken_HK
dc.contributor.authorIp, NYen_HK
dc.date.accessioned2012-03-23T09:49:47Z-
dc.date.available2012-03-23T09:49:47Z-
dc.date.issued2008en_HK
dc.identifier.citationJournal Of Neuroscience, 2008, v. 28 n. 19, p. 4872-4877en_HK
dc.identifier.issn0270-6474en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145816-
dc.description.abstractAccumulating evidence indicates that deregulation of cyclin-dependent kinase 5 (Cdk5) activity is associated with apoptosis in various neurodegenerative disease models. Interestingly, recent studies suggest that Cdk5 may also favor neuronal survival. Nonetheless, whether Cdk5 is directly required for neuronal survival during development remains enigmatic. In the current study, we established the pivotal role of Cdk5 in neuronal survival during development by demonstrating that reduction or absence of Cdk5 activity markedly exacerbated neuronal death in cultures and in vivo. Interestingly, the antiapoptotic protein Bcl-2 (B-cell lymphoma protein 2) was identified as a novel substrate of Cdk5. We found that Cdk5-mediated phosphorylation of Bcl-2 at Ser70 was required for the neuroprotective effect of Bcl-2. Intriguingly, inhibition of this phosphorylation conferred proapoptotic property to Bcl-2. Furthermore, overexpression of a Bcl-2 mutant lacking the Cdk5 phosphorylation site abolished the protective effect of Cdk5 re-expression in Cdk5-/- neurons, suggesting that Ser70 phosphorylation of Bcl-2 contributed to Cdk5-mediated neuronal survival. Our observations revealed that Cdk5-mediated Bcl-2 phosphorylation is pivotal for the antiapoptotic effect of Bcl-2 and contributes to the maintenance of neuronal survival by Cdk5. Our study has also identified Cdk5 as a regulator of Bcl-2 function in neuronal apoptosis. Copyright © 2008 Society for Neuroscience.en_HK
dc.languageengen_US
dc.publisherSociety for Neuroscience. The Journal's web site is located at http://www.jneurosci.orgen_HK
dc.relation.ispartofJournal of Neuroscienceen_HK
dc.subjectChemicals And Cas Registry Numbers: Protein Bcl 2, 219306-68-0en_US
dc.subjectSerine, 56-45-1, 6898-95-9en_US
dc.subjectCyclin-Dependent Kinase 5, Ec 2.7.1.37en_US
dc.subjectNeuroprotective Agentsen_US
dc.subjectProto-Oncogene Proteins C-Bcl-2en_US
dc.subject.meshAnimalsen_HK
dc.subject.meshApoptosis - physiologyen_HK
dc.subject.meshCell Survival - physiologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCyclin-Dependent Kinase 5 - deficiency - metabolism - physiologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMice, Knockouten_HK
dc.subject.meshNeurons - metabolism - physiologyen_HK
dc.subject.meshNeuroprotective Agents - metabolismen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProto-Oncogene Proteins c-bcl-2 - metabolism - physiologyen_HK
dc.subject.meshRetinal Ganglion Cells - metabolism - physiologyen_HK
dc.subject.meshSubstrate Specificityen_HK
dc.titleCyclin-dependent kinase 5 supports neuronal survival through phosphorylation of Bcl-2en_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, ZH:zelda@hku.hken_HK
dc.identifier.authorityCheung, ZH=rp01588en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1523/JNEUROSCI.0689-08.2008en_HK
dc.identifier.pmid18463240-
dc.identifier.scopuseid_2-s2.0-44949105375en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44949105375&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue19en_HK
dc.identifier.spage4872en_HK
dc.identifier.epage4877en_HK
dc.identifier.eissn1529-2401-
dc.identifier.isiWOS:000255681500006-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridCheung, ZH=6507483375en_HK
dc.identifier.scopusauthoridGong, K=36900598600en_HK
dc.identifier.scopusauthoridIp, NY=7005756760en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats