Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis.
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Agami R, Blandino G, Oren M, Shaul Y
Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis.
Nature. 1999 Jun 24;399(6738):809-13.
- PubMed ID
- 10391250 [ View in PubMed]
- 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-Abl. p73, a member of the p53 family of tumour-suppressor proteins, can also induce apoptosis. Here we show that the apoptotic activity of p73alpha requires the presence of functional, kinase-competent c-Abl. Furthermore, p73 and c-Abl can associate with each other, andthis 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 to phosphorylate p73 is markedly increased by gamma-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.