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DNA‐damage‐responsive acetylation of pRb regulates binding to E2F‐1
Author(s) -
Markham Douglas,
Munro Shonagh,
Soloway Judith,
O'Connor Darran P,
La Thangue Nicholas B
Publication year - 2006
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400591
Subject(s) - acetylation , retinoblastoma protein , e2f , dna damage , cyclin dependent kinase , microbiology and biotechnology , phosphorylation , chemistry , histone , biology , cancer research , dna , biochemistry , cell cycle , gene
The pRb (retinoblastoma protein) tumour suppressor protein has a crucial role in regulating the G1‐ to S‐phase transition, and its phosphorylation by cyclin‐dependent kinases is an established and important mechanism in controlling pRb activity. In addition, the targeted acetylation of lysine (K) residues 873/874 in the carboxy‐terminal region of pRb located within a cyclin‐dependent kinase‐docking site hinders pRb phosphorylation and thereby retains pRb in an active state of growth suppression. Here, we report that the acetylation of pRb K873/874 occurs in response to DNA damage and that acetylation regulates the interaction between the C‐terminal E2F‐1‐specific domain of pRb and E2F‐1. These results define a new role for pRb acetylation in the DNA damage signalling pathway, and suggest that the interaction between pRb and E2F‐1 is controlled by DNA‐damage‐dependent acetylation of pRb.