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Acetylation of the p53 DNA-binding domain regulates apoptosis induction.
Open accessAbstract
The ability of p53 to induce apoptosis plays an important role in tumor suppression. Here, we describe a previously unknown posttranslational modification of the DNA-binding domain of p53. This modification, acetylation of lysine 120 (K120), occurs rapidly after DNA damage and is catalyzed by the MYST family acetyltransferases hMOF and TIP60. Mutation of K120 to arginine, as occurs in human cancer, debilitates K120 acetylation and diminishes p53-mediated apoptosis without affecting cell-cycle arrest. The K120R mutation selectively blocks the transcription of proapoptotic target genes such as BAX and PUMA while the nonapoptotic targets p21 and hMDM2 remain unaffected. Consistent with this, depletion of hMOF and/or TIP60 inhibits the ability of p53 to activate BAX and PUMA transcription. Furthermore, the acetyllysine 120 (acetyl-K120) form of p53 specifically accumulates at proapoptotic target genes. These data suggest that K120 acetylation may help distinguish the cell-cycle arrest and apoptotic functions of p53.
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“K120 resides within the p53 DNA-binding domain and its acetylation increases its binding affinity for the Bax and PUMA gene promoters, while simultaneously preventing binding to the promoter of p21 (Sykes et al., 2006; Tang Y. et al., 2006; Reed and Quelle, 2014).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Sykes et al., 2006
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Metadata
- Authors
- Sykes, S. M., Mellert, H. S., Holbert, M. A., Li, K., Marmorstein, R., Lane, W. S., & McMahon, S. B.
- Affiliations
- Thomas Jefferson University (US)
- The Wistar Institute (US)
- Harvard University (US)
- Corresponding author
- McMahon, Steven B.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 24
- Issue
- 6
- Pages
- 841-851
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC1766330
- OpenAlex
- W2038324148
- Cited by
- 752
- References
- 51
- Citations by year
- 2026: 22 · 2025: 28 · 2024: 25 · 2023: 24 · 2022: 31 · 2021: 39 · 2020: 29 · 2019: 30 · 2018: 38 · 2017: 31 · 2016: 43 · 2015: 44 · 2014: 45 · 2013: 52 · 2012: 52
- FWCI
- 21.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R01CA090465, CA090465, CA098172, R01CA098172)
- National Institute of General Medical Sciences (R01GM060293)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, DNA-binding domain, post-translational modification, apoptosis induction, hMOF, Tip60, p21, DNA damage response, tumor suppression, cell cycle arrest
- MeSH terms
- Lysine Acetyltransferase 5, Acetylation, Amino Acid Sequence, Binding Sites, Cell Cycle, Humans, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Tumor Suppressor Protein p53, Apoptosis, Apoptosis Regulatory Proteins, bcl-2-Associated X Protein, Histone Acetyltransferases
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