c-Abl tyrosine kinase regulates the human Rad9 checkpoint protein in response to DNA damage.
Mol Cell Biol
; 22(10): 3292-300, 2002 May.
Article
in En
| MEDLINE
| ID: mdl-11971963
ABSTRACT
The ubiquitously expressed c-Abl tyrosine kinase is activated in the apoptotic response of cells to DNA damage. The mechanisms by which c-Abl signals the induction of apoptosis are not understood. Here we show that c-Abl binds constitutively to the mammalian homolog of the Schizosaccharomyces pombe Rad9 cell cycle checkpoint protein. The SH3 domain of c-Abl interacts directly with the C-terminal region of Rad9. c-Abl phosphorylates the Rad9 Bcl-2 homology 3 domain (Tyr-28) in vitro and in cells exposed to DNA-damaging agents. The results also demonstrate that c-Abl-mediated phosphorylation of Rad9 induces binding of Rad9 to the antiapototic Bcl-x(L) protein. The regulation of Rad9 by c-Abl in the DNA damage response is further supported by the demonstration that the interaction between c-Abl and Rad9 contributes to DNA damage-induced apoptosis. These findings indicate that Rad9 is regulated by a c-Abl-dependent mechanism in the apoptotic response to genotoxic stress.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA Damage
/
Proto-Oncogene Proteins c-abl
/
Apoptosis
/
Cell Cycle Proteins
Limits:
Humans
Language:
En
Journal:
Mol Cell Biol
Year:
2002
Document type:
Article
Affiliation country:
United States