Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.

Abstract	We report the p35 and p60 forms of XRCC4 protein, appearing in human leukemia MOLT-4 or U937 cells following X-irradiation or hyperthermia. p35 appeared in conjunction with the cleavage of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and the fragmentation of internucleosomal DNA, and was suppressed by Ac-DEVD-CHO. p35 was also produced in vitro by treating MOLT-4 cell lysate with recombinant caspases, suggesting that p35 was a caspase-cleaved fragment of XRCC4 in apoptotic cell death. p60 was sensitive to treatment with phosphatase or wortmannin and was undetectable in M059J cells deficient in DNA-PKcs. However, p60 was found in ataxia-telangiectasia cells after irradiation. These results indicated p60 as a phosphorylated form of XRCC4, requiring DNA-PKcs but not ataxia-telangiectasia mutated (ATM).
Authors	Y Matsumoto, N Suzuki, N Namba, N Umeda, X J Ma, A Morita, M Tomita, A Enomoto, S Serizawa, K Hirano, K Sakaia, H Yasuda, Y Hosoi
Journal	FEBS letters (FEBS Lett) Vol. 478 Issue 1-2 Pg. 67-71 (Jul 28 2000) ISSN: 0014-5793 [Print] England
PMID	10922471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Androstadienes Caspase Inhibitors Cell Cycle Proteins DNA-Binding Proteins Nuclear Proteins Peptide Fragments Phosphoinositide-3 Kinase Inhibitors Recombinant Proteins Tumor Suppressor Proteins XRCC4 protein, human ATM protein, human Ataxia Telangiectasia Mutated Proteins DNA-Activated Protein Kinase PRKDC protein, human Protein Serine-Threonine Kinases CASP3 protein, human CASP7 protein, human Caspase 3 Caspase 7 Caspases Wortmannin
Topics	Androstadienes (pharmacology) Ataxia Telangiectasia Mutated Proteins Blotting, Western Caspase 3 Caspase 7 Caspase Inhibitors Caspases (metabolism) Cell Cycle Proteins DNA-Activated Protein Kinase DNA-Binding Proteins (chemistry, metabolism, radiation effects) Hot Temperature Humans Molecular Weight Nuclear Proteins Peptide Fragments (chemistry, metabolism, radiation effects) Phosphatidylinositol 3-Kinases (metabolism) Phosphoinositide-3 Kinase Inhibitors Phosphorylation (radiation effects) Protein Serine-Threonine Kinases (antagonists & inhibitors, deficiency, genetics, metabolism) Recombinant Proteins (antagonists & inhibitors, metabolism) Tumor Cells, Cultured Tumor Suppressor Proteins U937 Cells Wortmannin

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