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- W1995262004 abstract "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." @default.
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- W1995262004 date "2010-04-01" @default.
- W1995262004 modified "2023-10-16" @default.
- W1995262004 title "G-protein-coupled Receptor Kinase 5 Phosphorylates p53 and Inhibits DNA Damage-induced Apoptosis" @default.
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- W1995262004 doi "https://doi.org/10.1074/jbc.m109.094243" @default.
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