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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6738
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pubmed:dateCreated |
1999-7-21
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pubmed:abstractText |
The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents and contributes to the induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms. Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage.
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pubmed:commentsCorrections |
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
399
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
814-7
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10391251-Animals,
pubmed-meshheading:10391251-Apoptosis,
pubmed-meshheading:10391251-Binding Sites,
pubmed-meshheading:10391251-COS Cells,
pubmed-meshheading:10391251-Cell Line,
pubmed-meshheading:10391251-DNA Damage,
pubmed-meshheading:10391251-DNA-Binding Proteins,
pubmed-meshheading:10391251-Genes, Tumor Suppressor,
pubmed-meshheading:10391251-Mice,
pubmed-meshheading:10391251-Nuclear Proteins,
pubmed-meshheading:10391251-Phosphorylation,
pubmed-meshheading:10391251-Protein Binding,
pubmed-meshheading:10391251-Proto-Oncogene Proteins c-abl,
pubmed-meshheading:10391251-Recombinant Proteins,
pubmed-meshheading:10391251-Tumor Suppressor Proteins,
pubmed-meshheading:10391251-src Homology Domains
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pubmed:year |
1999
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pubmed:articleTitle |
p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage.
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pubmed:affiliation |
Department of Cancer Cell Biology, Harvard School of Public Health, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article
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