c-Abl Tyrosine Kinase Selectively Regulates p73 Nuclear Matrix Association

• Published in: The Journal of biological chemistry 2003-09, Vol.278 (36), p.34475-34482
• Main Authors: Ben-Yehoyada, Merav, Ben-Dor, Israel, Shaul, Yosef
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Baculoviridae - metabolism; Cell Cycle; Cell Line; Cell Nucleus - metabolism; Cell Separation; Chromatin - chemistry; Chromatin - metabolism; COS Cells; DNA Damage; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Enzyme Activation; Flow Cytometry; Genes, Tumor Suppressor; Humans; Insecta; Nuclear Matrix - metabolism; Nuclear Proteins - metabolism; Phosphorylation; Precipitin Tests; Protein Binding; Protein Transport; Proto-Oncogene Proteins c-abl - metabolism; Radiation, Ionizing; Subcellular Fractions; Time Factors; Tumor Cells, Cultured; Tumor Protein p73; Tumor Suppressor Protein p53 - metabolism; Tumor Suppressor Proteins; Tyrosine - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M301051200

p73 is a structural and functional homologue of the p53 tumor-suppressor protein. Like p53, p73 is activated in response to DNA-damaging insults to induce cell cycle arrest or apoptosis. Under these conditions p73 is tyrosine-phosphorylated by c-Abl, a prerequisite modification for p73 to elicit cell death in fibroblasts. In this study we report that in response to ionizing radiation, p73 undergoes nuclear redistribution and becomes associated with the nuclear matrix. This association is c-Abl-dependent because it was not observed in cells that are defective in c-Abl kinase activation. Moreover, STI-571, a specific c-Abl kinase inhibitor, is sufficient to block significantly p73α nuclear matrix association. The observed c-Abl dependence of nuclear matrix association was recapitulated in the heterologous baculovirus system. Under these conditions p73α but not p53 is specifically tyrosine-phosphorylated by c-Abl. Moreover, the phosphorylated p73α is predominantly found in association with the nuclear matrix. Thus, in response to ionizing radiation p73 is modified in a c-Abl-dependent manner and undergoes nuclear redistribution and translocates to associate with the nuclear matrix. Our data describe a novel mechanism of p73 regulation.