MilliporeSigma
  • Heat shock protein gp96 decreases p53 stability by regulating Mdm2 E3 ligase activity in liver cancer.

Heat shock protein gp96 decreases p53 stability by regulating Mdm2 E3 ligase activity in liver cancer.

Cancer letters (2015-02-01)
Bo Wu, Xiaoyu Chu, Cong Feng, Junwei Hou, Hongxia Fan, Ningning Liu, Changfei Li, Xianping Kong, Xin Ye, Songdong Meng
ABSTRACT

The resistance to apoptosis displayed by liver cancer plays a key role in hepatocarcinogenesis, tumor progression, and resistance to chemo- or radio-therapy. In this study, we uncovered the potential role and mechanism of heat shock protein gp96 in regulating liver tumor cell growth and apoptosis. P53 protein was identified as a gp96 client protein by profiling apoptosis-related proteins in gp96-knockdown liver cancer cells. Overexpression and knockdown studies both demonstrated that gp96 decreases p53 protein levels, and gp96 regulated cell apoptosis in a p53-dependent manner. We further provide evidence that gp96 interacts with both p53 and Mdm2 to enhance Mdm2-mediated p53 ubiquitination and degradation. Moreover, targeting gp96 with siRNA induced cell apoptosis and led to the suppression of liver tumor growth in vivo. In conclusion, we elucidated an underlying mechanism by which gp96 promotes p53 degradation via increasing Mdm2 E3 ligase activity and provided a new therapeutic strategy to target the gp96-mediated anti-apoptotic characteristic of hepatocellular carcinoma.

MATERIALS
Product Number
Brand
Product Description

Supelco
Cycloheximide, PESTANAL®, analytical standard
Sigma-Aldrich
Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, Suitable for cell culture
Sigma-Aldrich
Cycloheximide, ≥90% (HPLC)
Millipore
Cycloheximide solution, 0.1%, suitable for microbiology
Cisplatin impurity A, European Pharmacopoeia (EP) Reference Standard
USP
Transplatin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Cycloheximide, Biotechnology Performance Certified
Sigma-Aldrich
Cycloheximide, from microbial, ≥94% (TLC)
Cisplatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Sigma-Aldrich
trans-Platinum(II)diammine dichloride