p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA damage

Autor:	Hisashi Shioya, Donald Kufe, Xiangao Sun, Yinyin Huang, Surender Kharbanda, Hua Lu, Zhi-Min Yuan, Ralph R. Weichselbaum, Jijie Gu, Takatoshi Ishiko
Rok vydání:	1999
Předmět:	Programmed cell death Multidisciplinary DNA damage Biology Molecular biology SH3 domain hemic and lymphatic diseases Tumor Protein p73 Tyrosine Signal transduction skin and connective tissue diseases neoplasms Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src
Zdroj:	Nature. 399:814-817
ISSN:	1476-4687 0028-0836
DOI:	10.1038/21704
Popis:	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 damage1,2. The tyrosine kinase c-Abl is activated by certain DNA-damaging agents3 and contributes tothe induction of programmed cell death (apoptosis) by p53-dependent and p53-independent mechanisms4. 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::00a1d8ae10f6c60794f568c32f8ad311 https://doi.org/10.1038/21704 Zobrazit plný text záznamu Plný text ve formátu PDF