Linked Life Data

19176998

Source:http://linkedlifedata.com/resource/pubmed/id/19176998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-2-13
pubmed:abstractText
We have previously shown that Chk2 stability, which is increased after DNA damage in some cells, is regulated in part through phosphorylation at S456 and that a mutant Chk2 (S456A) is hyperubiquitinated and turned over more rapidly than wild-type Chk2.(1) Here we show that the S456A mutant preferentially binds to Mdm2 compared to wild-type Chk2 and downregulation of Mdm2 with siRNA can rescue the observed destabilization of S456A Chk2 following DNA damage. Ubiquitination of wild-type Chk2 is increased by co-expression of Mdm2, and increasing amounts of Mdm2 enhance degradation of both wild-type and mutant S456A Chk2. Surprisingly, however, an E3 ligase defective version of Mdm2 (DeltaC7) also increases ubiquitination and degradation of Chk2 when transfected into cells, suggesting that the ability of Mdm2 to affect Chk2 turnover is independent of its intrinsic E3 ligase function. Recently the acetyltransferase PCAF was shown to have intrinsic E3 ligase activity against itself and Mdm2. We found that PCAF interacts with both Mdm2 and Chk2 and that PCAF increases Chk2 ubiquitination and degradation. Interestingly as well, a PCAF deletion mutant that lacks E3 ligase activity towards Mdm2 also enhances Chk2 degradation. We hypothesize that Mdm2 and PCAF may function as part of a multi-subunit E3 complex in their regulation of Chk2 turnover.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
430-7
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Mdm2 and PCAF increase Chk2 ubiquitination and degradation independently of their intrinsic E3 ligase activities.
pubmed:affiliation
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural