Linked Life Data

12857758

Source:http://linkedlifedata.com/resource/pubmed/id/12857758

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2003-9-22
pubmed:abstractText
DNA damage is a key initiator of neuronal death. We have previously shown that the tumor suppressor p53, in conjunction with cyclin-dependent kinases (CDKs), regulates the mitochondrial pathway of death in neurons exposed to genotoxic agents. However, the mechanisms by which p53 is regulated is unclear. Presently, we show that p53 is phosphorylated on Ser-15 following DNA damage and this occurs independently of the CDK pathway. Instead, we show that p53 phosphorylation, stability, as well as neuronal death is regulated, in part, by the ataxia telangiectasia-mutated (ATM) protein. Previous reports have suggested that ATM regulation of p53 occurs through Chk2. However, in our present paradigms, we show that ATM functions separately from Chk2 to regulate p53 stability and neuronal death. Chk2 deficiency does not affect p53 stability or neuronal death induced by Topoisomerase I or II inhibition. Taken together, our results provide a model by which DNA damage can activate an ATM-dependent, Chk2-independent pathway of p53-mediated neuronal death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
37782-9
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Ataxia telangiectasia-mutated protein can regulate p53 and neuronal death independent of Chk2 in response to DNA damage.
pubmed:affiliation
Neuroscience Research Program of Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't