DNA-damage-responsive acetylation of pRb regulates binding to E2F-1 |
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| Authors: | Markham Douglas Munro Shonagh Soloway Judith O'Connor Darran P La Thangue Nicholas B |
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| Affiliation: | Laboratory of Cancer Biology, Nuffield Department of Clinical Laboratory Sciences, Medical Sciences Division, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. |
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| Abstract: | 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. |
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