Article
- The EMBO Journal (2007) 26, 2083 - 2093
- doi:10.1038/sj.emboj.7601652
Published online: 22 March 2007
Subject Categories:
Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage
Yasumichi Inoue1,2, Masatoshi Kitagawa3 and Yoichi Taya1,2
- Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan
- SORST, Japan Science and Technology Agency, Tokyo, Japan
- Department of Biochemistry 1, Hamamatsu University School of Medicine, Hamamatsu, Japan
Correspondence to:
Yoichi Taya, Radiobiology Division, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. Tel.: +81 3 3542 2511, ext. 4800; Fax: +81 3 5565 0727; E-mail: ytaya@gan2.res.ncc.go.jp
Received 12 August 2006; Accepted 21 February 2007
Abstract
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.
Keywords:
- Cdk,
- Chk1,
- Chk2,
- E2F,
- RB
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