Deciphering the acetylation code of p53 in transcription regulation and tumor suppression
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Although it is well-established that p53-mediated tumor suppression mainly acts through its ability in transcriptional regulation, the molecular mechanisms of this regulation are not completely understood. Among a number of regulatory modes, acetylation of p53 attracts great interests. p53 was one of the first non-histone proteins found to be functionally regulated by acetylation and deacetylation, and subsequent work has established that reversible acetylation is a general mechanism for regulation of non-histone proteins. Unlike other types of posttranslational modifications occurred during stress responses, the role of p53 acetylation has been recently validated in vivo by using the knock-in mice with both acetylation-defective and acetylation-mimicking p53 mutants. Here, we review the role of acetylation in p53-mediated activities, with a focus on which specific acetylation sites are critical for p53-dependent transcription regulation during tumor suppression and how acetylation of p53 recruits specific "readers" to execute its promoter-specific regulation of different targets. We also discuss the role of p53 acetylation in differentially regulating its classic activities in cell cycle arrest, senescence and apoptosis as well as newly identified unconventional functions such as cell metabolism and ferroptosis.
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p53 has 13 known acetylation sites attributable to at least six different KATs and KDACs.
“13 known acetylation sites on p53 are attributable to the activity of at least six different KATs and KDACs [44,45].”
From Acetylation: a new target for protein degradation in cancer (2025) · cites this paper as [45]
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Insights into regulators of p53 acetylation
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Functional investigations of p53 acetylation enabled by heterobifunctional molecules
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- Authors
- Xia, Z., Kon, N., Gu, A. P., Tavana, O., & Gu, W.
- Affiliations
- Herbert Irving Comprehensive Cancer Center (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Gu, Wei
- Venue
- Oncogene
- Published
- 2022-04-29
- Volume
- 41
- Issue
- 22
- Pages
- 3039-3050
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC9149126
- OpenAlex
- W4225101492
- Cited by
- 60
- References
- 132
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 7 · 2023: 10 · 2022: 9
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (R35CA253059, RO1CA258390, R01CA254970)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- p53, protein acetylation, deacetylation, transcriptional regulation, tumor suppression, acetylation sites, cell cycle arrest, cellular senescence, apoptosis, cellular metabolism, ferroptosis
- MeSH terms
- Acetylation, Animals, Humans, Neoplasms, Protein Processing, Post-Translational, Tumor Suppressor Protein p53, Apoptosis, Mice, Cell Cycle Checkpoints
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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