DNA‐damage‐responsive acetylation of pRb regulates binding to E2F‐1
Open accessAbstract
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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DNA damage increases acetylation of human RB at lysines 873 and 874, decreasing RB phosphorylation by cyclin-Cdk complexes and increasing repression of E2F1.
“DNA damage increases the acetylation of human RB at lysines 873 and 874, which decreases RB phosphorylation by cyclin–Cdk (cyclin-dependent kinase) complexes and therefore increases its repression over E2F1 (REF. 77).”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [77]
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- Authors
- Markham, D., Munro, S., Soloway, J., O'Connor, D. P., & La Thangue, N. B.
- Affiliations
- John Radcliffe Hospital (GB)
- ORCID
- Munro, Shonagh
- Venue
- The EMBO Reports
- Published
- 2006-02-01
- Volume
- 7
- Issue
- 2
- Pages
- 192-198
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC1369245
- OpenAlex
- W2114208687
- Cited by
- 62
- References
- 27
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 4
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- EMBO Reports (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK (13058)
- Research Councils UK
- European Commission
- Medical Research Council
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- retinoblastoma protein, lysine acetylation, E2F1, DNA damage response, protein-protein interaction, G1/S transition, cell cycle regulation, tumour suppressor
- MeSH terms
- Acetylation, Animals, Cell Nucleus, DNA Damage, Etoposide, Fluorescent Dyes, Gene Expression Regulation, Humans, Indoles, Luciferases, Models, Biological, Nuclear Proteins, Transfection, Retinoblastoma Protein, Protein Structure, Tertiary, Nucleic Acid Synthesis Inhibitors, NIH 3T3 Cells, Cell Line, Tumor, E2F1 Transcription Factor, Mice
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