Gain of function of mutant p53: The mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation
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This article investigates the mechanistic aspects of mutant p53 "gain of function" in response to DNA damage. We show that mutant forms of p53 protein interact with NF-Y. The expression of cyclin A, cyclin B1, cdk1, and cdc25C, as well as the cdk1-associated kinase activities, is upregulated after DNA damage, provoking a mutant p53/NF-Y-dependent increase in DNA synthesis. Mutant p53 binds NF-Y target promoters and, upon DNA damage, recruits p300, leading to histone acetylation. The recruitment of mutant p53 to the CCAAT sites is severely impaired upon abrogation of NF-YA expression. Endogenous NF-Y, mutant p53, and p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant transcriptional regulation underlies the ability of mutant p53 proteins to act as oncogenic factors.
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GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression.
“In contrast to wt-p53, GOF mut-p53 exhibits interactions with distinct transcription factors (e.g., NF-ɣ, SREBP, VDR, Sp1, ETS2, NFR2, p73, p63) that promote tumor initiation and progression [13,72,73,74,75,76,77].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [74]
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- Authors
- Di Agostino, S., Strano, S., Emiliozzi, V., Zerbini, V., Mottolese, M., Sacchi, A., Blandino, G., & Piaggio, G.
- Affiliations
- Instituto Nazionale Tumori Regina Elena (IT)
- Corresponding author
- Blandino, Giovanni
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 10
- Issue
- 3
- Pages
- 191-202
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2041383414
- Cited by
- 418
- References
- 0
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 18 · 2023: 19 · 2022: 15 · 2021: 25 · 2020: 24 · 2019: 19 · 2018: 23 · 2017: 27 · 2016: 34 · 2015: 26 · 2014: 35 · 2013: 18 · 2012: 23
- FWCI
- 9.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- 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 › Chromatin Remodeling and Cancer
- Keywords
- mutant p53, gain-of-function, NF-Y, P300, histone acetylation, DNA damage response, cell cycle regulation, cyclin A, cyclin B1, CDK1, Cdc25C, transcriptional regulation, oncogenic p53
- MeSH terms
- Base Sequence, Cell Cycle, DNA Damage, Humans, Mutation, Protein Binding, Transcription, Genetic, Tumor Suppressor Protein p53, CCAAT-Binding Factor, Cell Line, Tumor, p300-CBP Transcription Factors
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