Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting

被引:438
作者
Borrero, Liz J. Hernandez [1 ,2 ,3 ,4 ,5 ]
El-Deiry, Wafik S. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Brown Univ, Warren Alpert Med Sch, Lab Translat Oncol & Expt Canc Therapeut, Providence, RI 02912 USA
[2] Brown Univ, Warren Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA
[3] Brown Univ, Joint Program Canc Biol, Providence, RI 02912 USA
[4] Lifespan Hlth Syst, Providence, RI 02912 USA
[5] Brown Univ, Canc Ctr, Warren Alpert Med Sch, Providence, RI 02912 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER | 2021年 / 1876卷 / 01期
关键词
p53; CDKN1A; DR5; Puma; miRNA; Cell cycle; Apoptosis; Cancer; Therapeutics; DAMAGE-INDUCED PHOSPHORYLATION; DNA-BINDING DOMAIN; GAIN-OF-FUNCTION; PROLINE-RICH DOMAIN; CELL-CYCLE ARREST; WILD-TYPE P53; MUTANT P53; DOWN-REGULATION; CANCER-CELLS; GENE-EXPRESSION;
D O I
10.1016/j.bbcan.2021.188556
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
TP53 is the most commonly mutated gene in human cancer with over 100,000 literature citations in PubMed. This is a heavily studied pathway in cancer biology and oncology with a history that dates back to 1979 when p53 was discovered. The p53 pathway is a complex cellular stress response network with multiple diverse inputs and downstream outputs relevant to its role as a tumor suppressor pathway. While inroads have been made in understanding the biology and signaling in the p53 pathway, the p53 family, transcriptional readouts, and effects of an array of mutants, the pathway remains challenging in the realm of clinical translation. While the role of mutant p53 as a prognostic factor is recognized, the therapeutic modulation of its wild-type or mutant activities remain a work-in-progress. This review covers current knowledge about the biology, signaling mechanisms in the p53 pathway and summarizes advances in therapeutic development.
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页数:14
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