title: Essential Roles of E3 Ubiquitin Ligases in p53 Regulation.
abstract: The ubiquitination pathway and proteasomal degradation machinery dominantly regulate p53 tumor suppressor protein stability, localization, and functions in both normal and cancerous cells. Selective E3 ubiquitin ligases dominantly regulate protein levels and activities of p53 in a large range of physiological conditions and in response to cellular changes induced by exogenous and endogenous stresses. The regulation of p53's functions by E3 ubiquitin ligases is a complex process that can lead to positive or negative regulation of p53 protein in a context- and cell type-dependent manner. Accessory proteins bind and modulate E3 ubiquitin ligases, adding yet another layer of regulatory control for p53 and its downstream functions. This review provides a comprehensive understanding of p53 regulation by selective E3 ubiquitin ligases and their potential to be considered as a new class of biomarkers and therapeutic targets in diverse types of cancers.
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069, USA. Sanam.sane@usd.edu.
authors.forename: Sanam
authors.initials: S
authors.lastname: Sane
authors.affiliation: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069, USA. Khosrow.Rezvani@usd.edu.
authors.forename: Khosrow
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases
keywords: E3 ubiquitin ligases; apoptosis; cancer therapy; p53 tumor suppressor protein; tumor