Role of p53 circuitry in tumorigenesis: A brief review

被引:51
作者
Niazi, Sarfaraj [1 ]
Purohit, Madhusudan [1 ]
Niazi, Javed H. [2 ]
机构
[1] JSS Acad Higher Educ & Res, JSS Coll Pharm Mysuru, Dept Pharmaceut Chem, Mysuru 570015, India
[2] Sabanci Univ, SUNUM Nanotechnol Res Ctr, TR-34956 Istanbul, Turkey
关键词
p53; miRNA; Mdm2; Pirh2; COP1; Ubiquitin; Proteasome; Modulators; Pharmacophore; PROTEIN-PROTEIN INTERACTION; SMALL-MOLECULE INHIBITORS; STRUCTURE-BASED DESIGN; TUMOR-SUPPRESSOR P53; E3 UBIQUITIN LIGASE; DOUBLE MINUTE 2; MDM2-P53; INTERACTION; P53-MDM2; IN-VIVO; MUTANT P53;
D O I
10.1016/j.ejmech.2018.08.099
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Maintenance of genome integrity under the stressed condition is paramount for normal functioning of cells in the multicellular organisms. Cells are programmed to protect their genome through specialized adaptive mechanisms which will help decide their fate under stressed conditions. These mechanisms are the outcome of activation of the intricate circuitries that are regulated by the p53 master protein. In this paper, we provided a comprehensive review on p53, p53 homologues and their isoforms, including a description about the ubiquitin-proteasome system emphasizing its role in p53 regulation. p53 induced E3(Ub)-ligases are an integral part of the ubiquitin-proteasome system. This review outlines the roles of important E3(Ub)-ligases and their splice variants in maintaining cellular p53 protein homeostasis. It also covers up-to-date and relevant information on small molecule Mdm2 inhibitors originated from different organizations. The review ends with a discussion on future prospects and investigation directives for the development of next-generation modulators as p53 therapeutics. (C) 2018 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:7 / 24
页数:18
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