Cited by 308Cancer-related Molecular PathwaysPI3K/AKT/mTOR signaling in cancerCancer Mechanisms and Therapy

Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy

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Yue, Xuetian, Zhao, Yuhan, Xu, Yang, Zheng, Min, Feng, Zhaohui, Hu, Wenwei·2017·Journal of Molecular Biology

Abstract

Tumor suppressor p53 plays a central role in tumor suppression. p53 is the most frequently mutated gene in human cancer, and over half of human cancers contain p53 mutations. Majority of p53 mutations in cancer are missense mutations, leading to the expression of full-length mutant p53 (mutp53) protein. While the critical role of wild-type p53 in tumor suppression has been firmly established, mounting evidence has demonstrated that many tumor-associated mutp53 proteins not only lose the tumor-suppressive function of wild-type p53 but also gain new activities to promote tumorigenesis independently of wild-type p53, termed gain-of-function. Mutant p53 protein often accumulates to very high levels in tumors, contributing to malignant progression. Recently, mutp53 has become an attractive target for cancer therapy. Further understanding of the mechanisms underlying mutp53 protein accumulation and gain-of-function will accelerate the development of targeted therapies for human cancer harboring mutp53. In this review, we summarize the recent advances in the studies on mutp53 protein accumulation and gain-of-function and targeted therapies for mutp53 in human cancer.

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Crossref · 10.1016/j.jmb.2017.03.030

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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 [73]

    The “Mutant p53 gain-of-function” section says mutant p53 interacts with TAp63, TAp73, NF-Y, SREBP, VDR, Sp1, ETS2 and NRF2, and links the latter interactions to tumor progression. It does not specifically say these transcription-factor interactions promote tumor initiation. The cited names are NF-Y and NRF2, rather than the printed NF-ɣ and NFR2. (LLM, conf=0.85)

    Experimental — accuracy not yet measured
  • As a result of disturbed regulatory checks and novel transcriptional activity, mut-p53 tends to localize and accumulate in the nucleus.

    “As a result of disturbed regulatory checks and novel transcriptional activity, mut-p53 tends to localize and accumulate in the nucleus [73].”

    From The p53 Pathway in Glioblastoma (2018) · cites this paper as [73]

    The “Mutant p53 gain-of-function” section says many tumor-associated mutant p53 proteins are mainly nuclear and can regulate transcription through mechanisms different from wild-type p53. The “Mutant p53 protein accumulation in tumors” section links accumulation to disrupted MDM2-mediated degradation. Neither section says that novel transcriptional activity causes nuclear localization or accumulation; the claim’s causal phrasing is therefore unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Yue, X., Zhao, Y., Xu, Y., Zheng, M., Feng, Z., & Hu, W.
Affiliations
  • Rutgers, The State University of New Jersey (US)
  • Second Affiliated Hospital of Zhejiang University (CN)
  • First Affiliated Hospital Zhejiang University (CN)
Corresponding author
  • Feng, Zhaohui
  • Hu, Wenwei
Venue
Journal of Molecular Biology
Publisher
Elsevier BV
Published
2017-06
Volume
429
Issue
11
Pages
1595-1606
ISSN
0022-2836 (ISSN-L)
OpenAlex
W2605051147
Cited by
308
References
130
Citations by year
2026: 14 · 2025: 27 · 2024: 25 · 2023: 36 · 2022: 39 · 2021: 54 · 2020: 40 · 2019: 29 · 2018: 38 · 2017: 6
FWCI
3.25
Type
journal article
Language
en
Open access
Locations
  • Journal of Molecular Biology (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (NIH) (1R01CA160558-01, 1R01CA203965)
  • DOD (W81XWH-16-1-0358)
  • NIH (R01CA143204)
  • Bush Medical Research Award
  • NJCCR Postdoctoral Fellowship Award
Topics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
Keywords
mutant p53, TP53 mutation, gain-of-function, missense mutations, p53 tumor suppressor, protein accumulation, carcinogenesis, malignant progression, targeted cancer therapy
MeSH terms
Animals, Disease Models, Animal, Humans, Neoplasms, Tumor Suppressor Protein p53, Mutation, Missense, Mutant Proteins, Carcinogenesis

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