SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle
Open accessAbstract
Sirtuin 7 (SIRT7), an NAD + -dependent deacetylase, plays vital roles in energy sensing, but the underlying mechanisms of action remain less clear. Here, we report that SIRT7 is required for p53-dependent cell-cycle arrest during glucose deprivation. We show that SIRT7 directly interacts with p300/CBP-associated factor (PCAF) and the affinity for this interaction increases during glucose deprivation. Upon binding, SIRT7 deacetylates PCAF at lysine 720 (K720), which augments PCAF binding to murine double minute (MDM2), the p53 E3 ubiquitin ligase, leading to accelerated MDM2 degradation. This effect results in upregulated expression of the cell-cycle inhibitor, p21 Waf1/Cip1 , which further leads to cell-cycle arrest and decreased cell viability. These data highlight the importance of the SIRT7–PCAF interaction in regulating p53 activity and cell-cycle progression during conditions of glucose deprivation. This axis may represent a new avenue to design effective therapeutics based on tumor starvation.
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The clinical efficacy of MDM2 inhibitors may mainly rely on reversible cell cycle arrest rather than direct induction of cell death through p53-dependent signaling pathway.
“Therefore, the clinical efficacy of MDM2 inhibitors may mainly rely on the reversible cell cycle arrest rather than direct induction of cell death through p53-dependent signaling pathway [89–91].”
From Targeting p53–MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials (2022) · cites this paper as [91]
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References 66 · Cited by 40
- Authors
- Lu, Y.-F., Xu, X.-P., Lu, X.-P., Zhu, Q., Liu, G., Bao, Y.-T., Wen, H., Li, Y.-L., Gu, W., & Zhu, W.-G.
- Affiliations
- Shenzhen University (CN)
- Columbia University (US)
- Corresponding author
- Li, Ying-Lu
- Zhu, Wei-Guo
- Venue
- Oncogene
- Published
- 2020-05-13
- Volume
- 39
- Issue
- 24
- Pages
- 4650-4665
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC7286819
- OpenAlex
- W3025248465
- Cited by
- 40
- References
- 66
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 3
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Update notices
- correction (2026-07-01)
- Open access
- hybrid
- doi.org
- Locations
- Oncogene (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Shenzhen University (2017YFA0503900)
- Science and Technology Planning Project of Guangdong Province (2017B030301016)
- Northwest Fisheries Science Center
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Keywords
- SIRT7, p53, PCAF, MDM2 degradation, glucose deprivation, cell cycle arrest, protein deacetylation, p21, tumor starvation, NAD+-dependent deacetylase, p53 activation
- MeSH terms
- p300-CBP-Associated Factor, Glucose, Humans, Neoplasms, Tumor Suppressor Protein p53, Sirtuins, HCT116 Cells, p300-CBP Transcription Factors, Proto-Oncogene Proteins c-mdm2, Cell Cycle Checkpoints, Proteolysis
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