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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2001-1-26
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pubmed:abstractText |
DAP kinase is a pro-apoptotic calcium-regulated serine/threonine kinase, whose expression is frequently lost in human tumours. Here we show that DAP kinase counteracts oncogene-induced transformation by activating a p19ARF/p53-dependent apoptotic checkpoint. Ectopic expression of DAP kinase suppressed oncogenic transformation of primary embryonic fibroblasts by activating p53 in a p19ARF-dependent manner. Consequently, the fibroblasts underwent apoptosis, characterized by caspase activation and DNA fragmentation. In response to c-Myc or E2F-1, the endogenous DAP kinase protein was upregulated. Furthermore, functional or genetic inactivation of the endogenous DAP kinase reduced the extent of induction of p19ARF/p53 and weakened the subsequent apoptotic responses to c-Myc or E2F-1. These results establish a role for DAP kinase in an early apoptotic checkpoint designed to eliminate pre-malignant cells during cancer development.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Arid4a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma-Binding Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor DP1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p14ARF,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/death-associated protein kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1465-7392
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11146619-Animals,
pubmed-meshheading:11146619-Apoptosis,
pubmed-meshheading:11146619-Apoptosis Regulatory Proteins,
pubmed-meshheading:11146619-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:11146619-Carrier Proteins,
pubmed-meshheading:11146619-Cell Cycle Proteins,
pubmed-meshheading:11146619-Cell Division,
pubmed-meshheading:11146619-Cell Line, Transformed,
pubmed-meshheading:11146619-Cell Transformation, Neoplastic,
pubmed-meshheading:11146619-DNA-Binding Proteins,
pubmed-meshheading:11146619-E2F Transcription Factors,
pubmed-meshheading:11146619-E2F1 Transcription Factor,
pubmed-meshheading:11146619-Fetus,
pubmed-meshheading:11146619-Fibroblasts,
pubmed-meshheading:11146619-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11146619-Genes, Tumor Suppressor,
pubmed-meshheading:11146619-Genes, cdc,
pubmed-meshheading:11146619-Genes, myc,
pubmed-meshheading:11146619-Mice,
pubmed-meshheading:11146619-Mice, Knockout,
pubmed-meshheading:11146619-Oncogenes,
pubmed-meshheading:11146619-Proteins,
pubmed-meshheading:11146619-Retinoblastoma-Binding Protein 1,
pubmed-meshheading:11146619-Signal Transduction,
pubmed-meshheading:11146619-Transcription Factor DP1,
pubmed-meshheading:11146619-Transcription Factors,
pubmed-meshheading:11146619-Tumor Suppressor Protein p14ARF,
pubmed-meshheading:11146619-Tumor Suppressor Protein p53
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pubmed:year |
2001
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pubmed:articleTitle |
DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation.
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pubmed:affiliation |
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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