Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-1-12
pubmed:abstractText
The cellular level of the CDC25A phosphatase is tightly regulated during both the normal and genotoxic-perturbed cell cycle. Here, we describe a caspase-dependent cleavage of this protein at residue D223 in non-genotoxic apoptotic conditions. This specific proteolysis generates a catalytically active C-terminal fragment that localizes to the nuclear compartment. Accumulation of this active CDC25A fragment leads to reduced inhibitory phosphorylation of the CDC25A substrate cyclin-dependent kinase 2 (CDK2) on Tyr15. Moreover, CDK2 was found stably associated with this fragment, as well as with an ectopically expressed CDC25A224-525 truncation mutant that mimicks the cleavage product. Ectopic expression of this mutant induced CDK2 Tyr15 dephosphorylation, whereas its catalytically inactive version did not. Finally, this 224-525 mutant initiated apoptosis when transfected into HeLa cells, whereas its catalytic inactive form did not. Altogether, this study demonstrates for the first time that caspase-dependent cleavage of CDC25A is a central step linking CDK2 activation with non-genotoxic apoptotic induction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
208-18
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A caspase-dependent cleavage of CDC25A generates an active fragment activating cyclin-dependent kinase 2 during apoptosis.
pubmed:affiliation
Département Oncogenèse et Signalisation dans cellules Hématopoïétiques, INSERM U563-IFR30, Centre de Physiopathologie Toulouse-Purpan, CHU Purpan, 31024 Toulouse Cedex 3, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't