p16 Controls p53 Protein Expression Through miR-dependent Destabilization of MDM2

被引：15
作者：
Al-Khalaf, Huda H. [1 ,2 ]
Aboussekhra, Abdelilah [2 ]
机构：
[1] King Abdulaziz City Sci & Technol, Natl Ctr Genom Res, Riyadh, Saudi Arabia
[2] King Faisal Specialist Hosp & Res Ctr, Canc Biol & Expt Therapeut Sect, Dept Mol Oncol, MBC 03,Box 3354, Riyadh 11211, Saudi Arabia
来源：
MOLECULAR CANCER RESEARCH | 2018年 / 16卷 / 08期
关键词：
P16(INK4A) TUMOR-SUPPRESSOR; ONCOGENE-INDUCED SENESCENCE; CELL-CYCLE INHIBITION; ULTRAVIOLET-LIGHT; DNA-DAMAGE; ONCOPROTEIN MDM2; BREAST-CANCER; FIBROBLASTS; PATHWAY; PROGRESSION;
D O I：
10.1158/1541-7786.MCR-18-0017
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
p16(INK4A) and p53 are two major tumor suppressor proteins that are both upregulated in response to various cellular stresses and during senescence and aging. p53 is a well-characterized transcription factor, while p16(INK4A) a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene, and controls the expression of several genes through protein-protein interactions and also via miRNAs. This report demonstrates a p16(INK4A)-dependent positive regulation of p53 expression, at the protein level, in various human cells as well as in mouse embryonic fibroblasts. p16 suppresses p53 turnover through inhibition of its MDM2-related ubiquitination. This effect occurs through p16-related promotion of the MDM2 mRNA turnover via the p16(INK4A) downstream effectors miR-141 and miR-146b-5p, which bind specific sites at the 3' untranslated region of the MDM2 mRNA. (C) 2018 AACR.
引用
收藏
页码：1299 / 1308
页数：10
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