PMID: 26343143Sep 8, 2015Paper

Escape, or Vanish: Control the Fate of p53 through MDM2-Mediated Ubiquitination

Anti-cancer Agents in Medicinal Chemistry
Jinlian WeiQidong You

Abstract

p53 protein is a prominent tumor suppressor to induce cell cycle arrest, apoptosis and senescence, which attracts significant interest to cancer treatment. Therefore, it would be particularly important to restore the wild-type p53 that retains latent functions in the approximately 50% of tumors. MDM2 (murine double minute 2), the principal cellular antagonist of p53, has long been believed to suppress p53 activity through two main mechanisms: promoting degradation via its E3 ligase activity and masking p53 transcriptional activation by direct binding. Targeting MDM2 E3 ligase activity is becoming a potential antitumor strategy resulting from MDM2's decisive role in controlling the fate of p53: p53 is going to degradation when entrapped into MDM2-mediated ubiquitination, where p53 can escape by abrogating MDM2 E3 ligase activity using regulators. The intensive focus on regulating MDM2 ubiquitin E3 ligase activity has led to the rapid progress of its inhibitors, which may be possible to help p53 escape from degradation and restore its function to control tumor growth. This review summarizes the current inhibitors of MDM2 E3 ligase in cancer therapy based on the understanding the regulation of MDM2 E3 ubiquitin ligase activity, in...Continue Reading

Citations

Dec 1, 2017·International Journal of Molecular Sciences·Fahd BoutoujaHarald W Platta
May 26, 2017·Cell Death & Disease·Xiumei ZhangFeng Li
Sep 25, 2018·Technology in Cancer Research & Treatment·Bifeng ChenXianhong Feng
Sep 11, 2019·Cells·Hung-Chi YangDaniel Tsun-Yee Chiu
Aug 2, 2020·Clinics and Research in Hepatology and Gastroenterology·Mengqiong WuXin Liu

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