Abstract
c-Abl, a non-receptor tyrosine kinase, is activated by agents that damage DNA. This activation results in either arrest of the cell cycle in phase G1 or apoptotic cell death, both of which are dependent on the kinase activity of c-Abl1. p73, a member of the p53 family of tumour-suppressor proteins2,3, can also induce apoptosis3. Here we show that the apoptotic activity of p73α requires the presence of functional, kinase-competent c-Abl. Furthermore, p73 and c-Abl can associate with each other, and this binding is mediated by a PxxP motif in p73 and the SH3 domain of c-Abl. We find that p73 is a substrate of the c-Abl kinase and that the ability of c-Abl tophosphorylate p73 is markedly increased by γ-irradiation. Moreover, p73 is phosphorylated in vivo in response to ionizing radiation. These findings define a pro-apoptotic signalling pathway involving p73 and c-Abl.
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Acknowledgements
We thank W. J. Kaelin for the p73α plasmid; T. Kanda for the H2B-GFP plasmid; W.Jiang and T. Hunter for E-GFP; S. P. Goff for the Abi plasmids; and R. Bernards for allowing some of the work to be performed in his laboratory. This work was supported by the Israel Science Foundation founded by the Israel Academy of Sciences and Humanities (Y.S.), by the Ebner Family Biomedical Research Foundation at the Weizmann Institute of Science in Memory of Alfred and Dolfi Ebner (Y.S.), by the NCI (M.O.) and by Telethon (Italy) (G.B.).
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Agami, R., Blandino, G., Oren, M. et al. Interaction of c-Abl and p73α and their collaboration to induce apoptosis. Nature 399, 809–813 (1999). https://doi.org/10.1038/21697
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DOI: https://doi.org/10.1038/21697
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