|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
35
|
|
pubmed:dateCreated |
2005-8-19
|
|
pubmed:abstractText |
The p53 tumor suppressor gene is activated in response to DNA damage resulting in either growth arrest or apoptosis. We previously demonstrated the specific involvement of homeodomain interacting protein-kinase 2 (HIPK2), a nuclear serine/threonine kinase, in inducing p53-dependent apoptosis through selective p53 phosphorylation at serine 46 after severe genotoxic damage. Here we show that HIPK2 contributes to p53 regulation, independently from serine 46 phosphorylation upon nonapoptotic DNA damage such as that induced by cytostatic doses of cisplatin. We show that HIPK2 depletion by RNA interference inhibits p53 binding to the p21Waf1 promoter affecting its p53-induced transactivation thereby allowing cell proliferation. We found that nonapoptotic DNA damage induces p53 acetylation mediated by the HAT protein PCAF and this p53 post-translational modification is abolished by HIPK2 depletion. In this regard, we found that HIPK2 cooperates with PCAF to induce selectively p53 transcriptional activity toward the p21Waf1 promoter while depletion of either HIPK2 or PCAF abolished this function. These data show that HIPK2 regulates the p53 growth arrest function through its PCAF-mediated acetylation.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/HIPK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Acetyltransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/p300-CBP-associated factor
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
0950-9232
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
18
|
|
pubmed:volume |
24
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5431-42
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:15897882-Acetylation,
pubmed-meshheading:15897882-Antineoplastic Agents,
pubmed-meshheading:15897882-Apoptosis,
pubmed-meshheading:15897882-Blotting, Western,
pubmed-meshheading:15897882-Carrier Proteins,
pubmed-meshheading:15897882-Cell Cycle Proteins,
pubmed-meshheading:15897882-Cell Line, Tumor,
pubmed-meshheading:15897882-Cell Proliferation,
pubmed-meshheading:15897882-Cisplatin,
pubmed-meshheading:15897882-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15897882-DNA Damage,
pubmed-meshheading:15897882-Dose-Response Relationship, Drug,
pubmed-meshheading:15897882-Histone Acetyltransferases,
pubmed-meshheading:15897882-Humans,
pubmed-meshheading:15897882-Immunoprecipitation,
pubmed-meshheading:15897882-In Situ Nick-End Labeling,
pubmed-meshheading:15897882-Promoter Regions, Genetic,
pubmed-meshheading:15897882-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15897882-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15897882-Trans-Activators,
pubmed-meshheading:15897882-Transcription, Genetic,
pubmed-meshheading:15897882-Transcription Factors,
pubmed-meshheading:15897882-Transcriptional Activation,
pubmed-meshheading:15897882-Tumor Suppressor Protein p53,
pubmed-meshheading:15897882-p300-CBP Transcription Factors
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
HIPK2 contributes to PCAF-mediated p53 acetylation and selective transactivation of p21Waf1 after nonapoptotic DNA damage.
|
|
pubmed:affiliation |
Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
