Cited by 186Cancer-related Molecular PathwaysHeat shock proteins researchProtein Structure and Dynamics

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Reactivation of mutant p53: molecular mechanisms and therapeutic potential

Selivanova, G, Wiman, K G·2007·Oncogene

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Abstract

The p53 tumor suppressor gene is the most frequently mutated gene in cancer. Most p53 mutations are missense point mutations that cluster in the DNA-binding core domain. This results in distortion of core domain folding and disruption of DNA binding and transcriptional transactivation of p53 target genes. Structural studies have demonstrated that mutant p53 core domain unfolding is not irreversible. Mutant p53 is expressed at high levels in many tumors. Therefore, mutant p53 is a promising target for novel cancer therapy. Mutant p53 reactivation will restore p53-dependent apoptosis, resulting in efficient removal of tumor cells. A number of strategies for targeting mutant p53 have been designed, including peptides and small molecules that restore the active conformation and DNA binding to mutant p53 and induce p53-dependent suppression of tumor cell growth in vitro and in vivo. This opens possibilities for the clinical application of mutant p53 reactivation in the treatment of cancer.

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Authors: Selivanova, G., & Wiman, K. G.
Affiliations: Karolinska Institutet (SE)
Corresponding author: Wiman, K G
ORCID: Selivanova, G
Wiman, K G
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2007-04-02
Volume: 26
Issue: 15
Pages: 2243-2254
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1210295
OpenAlex: W2025977492
Cited by: 186
References: 105
Citations by year: 2026: 1 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 16 · 2015: 11 · 2014: 9 · 2013: 11 · 2012: 7
FWCI: 1.98
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
Funders: Cancerfonden
Karolinska Institutet
Cancerföreningen i Stockholm
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords: mutant p53, p53 reactivation, p53 tumor suppressor, missense mutations, protein unfolding, p53-dependent apoptosis, transcriptional activation, cancer therapy
MeSH terms: Humans, Mutation, Neoplasms, Protein Conformation, Tumor Suppressor Protein p53

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Reactivation of mutant p53: molecular mechanisms and therapeutic potential

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