Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2011-3-4
pubmed:abstractText
The cyclin dependent kinase 5 (Cdk5)/p35 complex is essential for regulation of cell survival during development and in models of neuronal excitotoxicity. Dysregulation of Cdk5, by cleavage of its neuronal specific activators p35 and p39, has been implicated in various neurodegenerative disorders such as Alzheimer's disease, however targets of the complex that regulate neuronal survival physiologically and/or during pathogenesis are largely unknown. Since hypoxia is a key feature in the pathogenesis of several neuronal disorders we investigated a role for Cdk5/p35 in the neuronal hypoxic response. Our data show that hypoxia modulates the p35/Cdk5 complex in primary cortical neurons at the transcriptional and protein level. Furthermore hypoxic induction of Cdk5 activity correlates with Hif-1? stabilisation, and direct interaction between these proteins can occur. Importantly, we demonstrate that Cdk5-mediated signaling is involved in Hif-1? stabilisation since inhibition of Cdk5 by roscovitine abrogates Hif-1? accumulation and induces cell death. Taken together our results show that the Cdk5/p35 complex may significantly contribute to modulation of Hif-1? stabilisation and impact neuronal survival during oxygen deprivation. Thus this study highlights a new hypoxia-mediated signaling pathway and implicates the cytoskeleton as a potential regulator of Hif-1?.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-6240
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
1381
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-10
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Cdk5 interacts with Hif-1? in neurons: a new hypoxic signalling mechanism?
pubmed:affiliation
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't