Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness

dc.contributor.authorOlivos III, David J.
dc.contributor.authorMayo, Lindsey D.
dc.contributor.departmentDepartment of Microbiology & Immunology, IU School of Medicineen_US
dc.date.accessioned2017-06-19T17:24:39Z
dc.date.available2017-06-19T17:24:39Z
dc.date.issued2016-11-26
dc.description.abstractSince its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche. We will also examine p53 gain of function (GOF) roles in stemness. Mutant p53 (mutp53) GOFs that lead to survival, drug resistance and colonization are reviewed in the context of the acquisition of advantageous transformation processes, such as differentiation and dedifferentiation, epithelial-to-mesenchymal transition (EMT) and stem cell senescence and quiescence. Finally, we will conclude with therapeutic strategies that restore wild-type p53 (wtp53) function in cancer and CSCs, including RING finger E3 ligases and CSC maintenance. The mechanisms by which wtp53 and mutp53 influence stemness in non-malignant stem cells and CSCs or tumor-initiating cells (TICs) are poorly understood thus far. Further elucidation of p53's effects on stemness could lead to novel therapeutic strategies in cancer research.en_US
dc.identifier.citationOlivos, D. J., & Mayo, L. D. (2016). Emerging Non-Canonical Functions and Regulation by p53: p53 and Stemness. International Journal of Molecular Sciences, 17(12), 1982. http://doi.org/10.3390/ijms17121982en_US
dc.identifier.urihttps://hdl.handle.net/1805/13074
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/ijms17121982en_US
dc.relation.journalInternational Journal of Molecular Sciencesen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePMCen_US
dc.subjectMdm2en_US
dc.subjectCancer stem cell (CSC)en_US
dc.subjectColonizationen_US
dc.subjectmutant p53en_US
dc.subjectNicheen_US
dc.subjectNon-canonical functionen_US
dc.subjectNormal stem cellsen_US
dc.subjectp53en_US
dc.subjectRegulationen_US
dc.subjectSurvivalen_US
dc.subjectTranslational modificationsen_US
dc.titleEmerging Non-Canonical Functions and Regulation by p53: p53 and Stemnessen_US
dc.typeArticleen_US
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