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Small-molecule inhibitors of USP7 induce apoptosis through oxidative and endoplasmic reticulum stress in cancer cells

Authors
 Gibok Lee  ;  Taek-In Oh  ;  Ki Bum Um  ;  Hyeshin Yoon  ;  Jaekyoung Son  ;  Byeong Mo Kim  ;  Hong-Il Kim  ;  Hackyoung Kim  ;  Young Jun Kim  ;  Chang-Soo Lee  ;  Ji-Hong Lim 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.470(1) : 181-186, 2016 
Journal Title
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 
ISSN
 0006-291X 
Issue Date
2016
Abstract
USP7 is a deubiquitinating enzyme that involves the ubiquitin proteasome system (UPS) to maintain regulation of protein synthesis and degradation. The well-known substrate of USP7 is the Mdm2-p53 complex. In fact, several studies have reported that functional inhibition of USP7 induces cancer cell apoptosis through activation of p53. However, the contribution of oxidative or endoplasmic reticulum (ER) stress, which is commonly induced by inhibition of the UPS for USP7 inhibitor-mediated apoptosis in cancer cells, has not been investigated. In contrast to previous reports, we show that p53 is not critical during USP7 inhibitor-induced apoptosis in several cancer cells. Inhibition of deubiquitinating enzyme activities by USP7 inhibitors causes ER stress by accumulating polyubiquitinated proteins in cancer cells. Furthermore, we demonstrate that USP7 inhibitors increase intracellular reactive oxygen species and mainly cause cancer cell apoptosis. Taken together, our results reveal that oxidative and ER stress, rather than the Mdm2-p53 axis, mainly contributes to USP7 inhibitor-mediated apoptosis in cancer cells.
Full Text
http://www.sciencedirect.com/science/article/pii/S0006291X16300213
DOI
10.1016/j.bbrc.2016.01.021
Appears in Collections:
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
Kim, Byeong Mo(김병모) ORCID logo https://orcid.org/0000-0002-0582-3132
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/155727
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