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rdf:type |
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lifeskim:mentions |
umls-concept:C0010531,
umls-concept:C0020792,
umls-concept:C0205314,
umls-concept:C0330390,
umls-concept:C0542341,
umls-concept:C0600499,
umls-concept:C0679622,
umls-concept:C0682323,
umls-concept:C0812244,
umls-concept:C0851285,
umls-concept:C1167622
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pubmed:issue |
17
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pubmed:dateCreated |
2005-4-25
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pubmed:abstractText |
Post-translational modifications play a crucial role in regulation of the protein stability and pro-apoptotic function of p53 as well as its close relative p73. Using a yeast two-hybrid screening based on the Sos recruitment system, we identified protein kinase A catalytic subunit beta (PKA-Cbeta) as a novel binding partner of p73. Co-immunoprecipitation and glutathione S-transferase pull-down assays revealed that p73alpha associated with PKA-Cbeta in mammalian cells and that their interaction was mediated by both the N- and C-terminal regions of p73alpha. In contrast, p53 failed to bind to PKA-Cbeta. In vitro phosphorylation assay demonstrated that glutathione S-transferase-p73alpha-(1-130), which has one putative PKA phosphorylation site, was phosphorylated by PKA. Enforced expression of PKA-Cbeta resulted in significant inhibition of the transactivation function and pro-apoptotic activity of p73alpha, whereas a kinase-deficient mutant of PKA-Cbeta had no detectable effect. Consistent with this notion, treatment with H-89 (an ATP analog that functions as a PKA inhibitor) reversed the dibutyryl cAMP-mediated inhibition of p73alpha. Of particular interest, PKA-Cbeta facilitated the intramolecular interaction of p73alpha, thereby masking the N-terminal transactivation domain with the C-terminal inhibitory domain. Thus, our findings indicate a PKA-Cbeta-mediated inhibitory mechanism of p73 function.
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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/CDKN1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/tumor suppressor protein p73
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
16665-75
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15723830-Animals,
pubmed-meshheading:15723830-Apoptosis,
pubmed-meshheading:15723830-Blotting, Western,
pubmed-meshheading:15723830-COS Cells,
pubmed-meshheading:15723830-Catalytic Domain,
pubmed-meshheading:15723830-Cell Cycle Proteins,
pubmed-meshheading:15723830-Cell Line,
pubmed-meshheading:15723830-Cell Line, Tumor,
pubmed-meshheading:15723830-Chromatin Immunoprecipitation,
pubmed-meshheading:15723830-Cyclic AMP,
pubmed-meshheading:15723830-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:15723830-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15723830-DNA Damage,
pubmed-meshheading:15723830-DNA-Binding Proteins,
pubmed-meshheading:15723830-Down-Regulation,
pubmed-meshheading:15723830-Genes, Tumor Suppressor,
pubmed-meshheading:15723830-Glutathione Transferase,
pubmed-meshheading:15723830-Humans,
pubmed-meshheading:15723830-Immunoblotting,
pubmed-meshheading:15723830-Immunoprecipitation,
pubmed-meshheading:15723830-Microscopy, Fluorescence,
pubmed-meshheading:15723830-Models, Genetic,
pubmed-meshheading:15723830-Nuclear Proteins,
pubmed-meshheading:15723830-Phosphorylation,
pubmed-meshheading:15723830-Protein Binding,
pubmed-meshheading:15723830-Protein Structure, Tertiary,
pubmed-meshheading:15723830-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15723830-Subcellular Fractions,
pubmed-meshheading:15723830-Transcriptional Activation,
pubmed-meshheading:15723830-Transfection,
pubmed-meshheading:15723830-Tumor Suppressor Protein p53,
pubmed-meshheading:15723830-Tumor Suppressor Proteins,
pubmed-meshheading:15723830-Two-Hybrid System Techniques
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pubmed:year |
2005
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pubmed:articleTitle |
Identification of protein kinase A catalytic subunit beta as a novel binding partner of p73 and regulation of p73 function.
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pubmed:affiliation |
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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