Interaction of c-Abl and p73 alpha and their collaboration to induce apoptosis

c-Abl, a non-receptor tyrosine kinase, is activated by agents that damage D NA. 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(1). p73, a member of the p53 family of tumour-suppressor proteins (2,3), can also induce apoptosis(3), Here we show that the apoptotic activi ty of p73 alpha requires the presence of functional, kinase-competent c-Abl . Furthermore, p73 and c-Abl can associate with each other, and this bindin g is mediated by a PxxP motif in p73 and the SH3 domain of c-Abl. We find t hat 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, p7 3 is phosphorylated in vivo in response to ionizing radiation. These findin gs define a pro-apoptotic signalling pathway involving p73 and c-Abl.