Premium
Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F‐1 after DNA damage
Author(s) -
Inoue Yasumichi,
Kitagawa Masatoshi,
Taya Yoichi
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601652
Subject(s) - biology , phosphorylation , dna damage , retinoblastoma protein , e2f , dna , chek1 , microbiology and biotechnology , cancer research , dna repair , cell cycle , genetics , biophysics , cell cycle checkpoint , cancer
The retinoblastoma tumor suppressor protein (pRB) plays a critical role in the control of cell proliferation and in the DNA damage checkpoints. pRB inhibits cell cycle progression through interactions with the E2F family of transcription factors. Here, we report that DNA damage induced not only the dephosphorylation of pRB at Cdk phosphorylation sites and the binding of pRB to E2F‐1, but also the phosphorylation of pRB at Ser612. Phosphorylation of pRB at Ser612 enhanced the formation of a complex between pRB and E2F‐1. Substitution of Ser612 with Ala decreased pRB–E2F‐1 binding and the transcriptional repression activity. Until now, Ser612 of pRB has been thought to be phosphorylated by Cdk2. However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM‐Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding of pRB to E2F‐1. These results suggest that Ser612 is phosphorylated by Chk1/2 after DNA damage, leading to the formation of pRB–E2F‐1. This is the first report that pRB is phosphorylated in vivo by a kinase other than Cdk.