The DOI matches its Crossref record; 49 of the 51 references it cites were found in a registry or an index.
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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Cites
WAF1, a potential mediator of p53 tumor suppression
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p53, the cellular gatekeeper for growth and division
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Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1×
“Alternatively, genes encoding other components of the p53 pathway can exhibit mutations (Vogelstein et al., 2000; Vousden and Lu, 2002).”
BackgroundEng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Activation of p53 Sequence-Specific DNA Binding by Acetylation of the p53 C-Terminal Domain
Gu, W., & Roeder, R. G. (1997) · Cell · doi:10.1016/s0092-8674(00)80521-8 · Cited by 2,559
Crystal Structure of a p53 Tumor Suppressor-DNA Complex: Understanding Tumorigenic Mutations
Cho, Y., Gorina, S., Jeffrey, P. D., & Pavletich, N. P. (1994) · Science · doi:10.1126/science.8023157 · Cited by 2,559 · cited 2×
“Loss of K120 acetylation specifically inhibits p53-mediated apoptosis Lysine 120 lies within a region of the DNA binding domain of p53 termed the L1 loop (Cho et al., 1994).”
Backgroundp53- and Drug-Induced Apoptotic Responses Mediated by BH3-Only Proteins Puma and Noxa
Villunger, A., Michalak, E. M., Coultas, L., Müllauer, F., Böck, G., Ausserlechner, M. J., Adams, J. M., & Strasser, A. (2003) · Science · doi:10.1126/science.1090072 · Cited by 1,327
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204
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2 of the 51 references couldn’t be matched to a known paper.
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Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610
Functions and mechanisms of non-histone protein acetylation
Narita, T., Weinert, B. T., & Choudhary, C. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0081-3 · Cited by 1,232
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222
The multiple mechanisms that regulate p53 activity and cell fate
Hafner, A., Bulyk, M. L., Jambhekar, A., & Lahav, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0110-x · Cited by 1,129
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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