Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 17, Pages 12823-12830Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.094243
Keywords
-
Categories
Funding
- Ministry of Science and Technology [2009ZX09303-006, 2009ZX09301-011, 2009CB522000]
- Natural Science Foundation of China [30830042, 30821002]
Ask authors/readers for more resources
G-protein-coupled receptor kinases (GRKs) are an important family of Ser/Thr kinases that specifically phosphorylate and desensitize the activated receptor in response to environmental stimulation. Here we identify p53, a key tumor suppressor, as a novel GRK substrate in vivo, revealing a previously unknown function of GRKs in regulation of genome stability. Knockdown GRK5 in osteosarcoma cells inhibits DNA damage-induced apoptosis via a p53-mediated mechanism. Furthermore, GRK5, but not GRK2 or GRK6, phosphorylates p53 at Thr-55, which promotes the degradation of p53, leading to inhibition of p53-dependent apoptotic response to genotoxic damage. Consistently, the increase of p53 and irradiation-induced apoptosis were observed in GRK5-deficient mice. These results demonstrate GRK5 as a novel kinase of p53, as well as a negative regulator of p53-mediated signal transduction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available