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- Title
p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage.
- Authors
Yuan, Z M; Shioya, H; Ishiko, T; Sun, X; Gu, J; Huang, Y Y; Lu, H; Kharbanda, S; Weichselbaum, R; Kufe, D
- Abstract
The protein p73 is a structural and functional homologue of the p53 tumour-suppressor protein but, unlike p53, it is not induced in response to DNA damage. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents and contributes to the induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms. Here we show that c-Abl binds to p73 in cells, interacting through its SH3 domain with the carboxy-terminal homo-oligomerization domain of p73. c-Abl phosphorylates p73 on a tyrosine residue at position 99 both in vitro and in cells that have been exposed to ionizing radiation. Our results show that c-Abl stimulates p73-mediated transactivation and apoptosis. This regulation of p73 by c-Abl in response to DNA damage is also demonstrated by a failure of ionizing-radiation-induced apoptosis after disruption of the c-Abl-p73 interaction. These findings show that p73 is regulated by a c-Abl-dependent mechanism and that p73 participates in the apoptotic response to DNA damage.
- Publication
Nature, 1999, Vol 399, Issue 6738, p814
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/21704