Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Dec 20;11(1):4.
doi: 10.3390/cancers11010004.

Regulators of Oncogenic Mutant TP53 Gain of Function

Satomi Yamamoto  1 , Tomoo Iwakuma  2   3
Affiliations
Review

Regulators of Oncogenic Mutant TP53 Gain of Function

Satomi Yamamoto et al. Cancers (Basel). .

Abstract

The tumor suppressor p53 (TP53) is the most frequently mutated human gene. Mutations in TP53 not only disrupt its tumor suppressor function, but also endow oncogenic gain-of-function (GOF) activities in a manner independent of wild-type TP53 (wtp53). Mutant TP53 (mutp53) GOF is mainly mediated by its binding with other tumor suppressive or oncogenic proteins. Increasing evidence indicates that stabilization of mutp53 is crucial for its GOF activity. However, little is known about factors that alter mutp53 stability and its oncogenic GOF activities. In this review article, we primarily summarize key regulators of mutp53 stability/activities, including genotoxic stress, post-translational modifications, ubiquitin ligases, and molecular chaperones, as well as a single nucleotide polymorphism (SNP) and dimer-forming mutations in mutp53.

Keywords: TP53; dimer-forming mutation; gain of function; molecular chaperone; mutant TP53; post-translational modification; single nucleotide polymorphism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mechanisms of mutant tumor suppressor p53 (mutp53) gain of function (GOF).
Figure 2
Figure 2
Environmental stresses alter stability and activity of mutant TP53 (mutp53) crucial for its oncogenic gain of function (GOF).
Figure 3
Figure 3
Upstream factors regulating mutant TP53 (mutp53) stability and activity, including post-translational modifications (PTMs) and molecular chaperones, as well as single nucleotide polymorphism 72 (SNP72) and dimer-forming mutations, in mutp53. TAD: Transactivation domain, PRR: Proline-rich region, DBD: DNA binding domain, NLS: Nuclear localization signal, OD: Oligomerization domain, NES: Nuclear export signal, CTD: C-terminal domain.
See this image and copyright information in PMC

References

    1. Vogelstein B., Lane D., Levine A.J. Surfing the p53 network. Nature. 2000;408:307–310. doi: 10.1038/35042675. - DOI - PubMed
    1. Kruiswijk F., Labuschagne C.F., Vousden K.H. p53 in survival, death and metabolic health: A lifeguard with a licence to kill. Nat. Rev. Mol. Cell Biol. 2015;16:393–405. doi: 10.1038/nrm4007. - DOI - PubMed
    1. Baugh E.H., Ke H., Levine A.J., Bonneau R.A., Chan C.S. Why are there hotspot mutations in the TP53 gene in human cancers? Cell Death Differ. 2018;25:154–160. doi: 10.1038/cdd.2017.180. - DOI - PMC - PubMed
    1. Soussi T., Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat. Rev. Cancer. 2001;1:233–240. doi: 10.1038/35106009. - DOI - PubMed
    1. Powell B., Soong R., Iacopetta B., Seshadri R., Smith D.R. Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer. Clin. Cancer Res. 2000;6:443–451. - PubMed