147 133

Cited 76 times in

Terpestacin inhibits tumor angiogenesis by targeting UQCRB of mitochondrial complex III and suppressing hypoxia-induced reactive oxygen species production and cellular oxygen sensing

Authors
 Hye Jin Jung  ;  Joong Sup Shim  ;  Jiyong Lee  ;  Young Mi Song  ;  Ki Chung Park  ;  Seung Hoon Choi  ;  Nam Doo Kim  ;  Jeong Hyeok Yoon  ;  Paul T. Mungai  ;  Paul T. Schumacker  ;  Ho Jeong Kwon 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.285(15) : 11584-11595, 2010 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2010
MeSH
Animals ; Bridged Bicyclo Compounds/pharmacology ; Carrier Proteins/metabolism* ; Electron Transport Complex III/metabolism* ; Endothelium, Vascular/cytology ; Female ; Hypoxia* ; Mice ; Mice, Inbred C3H ; Mitochondria/metabolism* ; Neoplasm Transplantation ; Neovascularization, Pathologic* ; Oxygen/metabolism* ; Reactive Oxygen Species* ; Vascular Endothelial Growth Factor A/metabolism
Abstract
Cellular oxygen sensing is required for hypoxia-inducible factor-1alpha stabilization, which is important for tumor cell survival, proliferation, and angiogenesis. Here we find that terpestacin, a small molecule previously identified in a screen of microbial extracts, binds to the 13.4-kDa subunit (UQCRB) of mitochondrial Complex III, resulting in inhibition of hypoxia-induced reactive oxygen species generation. Consequently, such inhibition blocks hypoxia-inducible factor activation and tumor angiogenesis in vivo, without inhibiting mitochondrial respiration. Overexpression of UQCRB or its suppression using RNA interference demonstrates that it plays a crucial role in the oxygen sensing mechanism that regulates responses to hypoxia. These findings provide a novel molecular basis of terpestacin targeting UQCRB of Complex III in selective suppression of tumor progression.
Files in This Item:
T201001439.pdf Download
DOI
10.1074/jbc.M109.087809
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Ki Cheong(박기청) ORCID logo https://orcid.org/0000-0002-3435-3985
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/166002
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse