The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis

被引：165

作者：

Pugh, CW ^{[1
]}

Ratcliffe, PJ ^{[1
]}

机构：

[1] Univ Oxford, Oxygen Sensing Grp, Oxford OX3 7BN, England

来源：

SEMINARS IN CANCER BIOLOGY | 2003年 / 13卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

HIF hypoxia; prolyl hydroxylase; ubiquitin; von Hippel-Lindau; tumour suppressor;

D O I：

10.1016/S1044-579X(02)00103-7

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Recently, work on the mechanism of action of the von Hippel-Lindau tumour suppressor protein (pVHL) and Studies on hypoxic gene regulation have converged, providing insights into both cellular oxygen sensing and cancer pathogenesis. pVHL is the recognition component of the E3-ubiquitin ligase complex involved in the degradation of hypoxia-inducible factor-1 (HIF) alpha-subunits. a process regulated by oxygen availability and blocked by disease causing pVHL mutations. In normoxic cells, pVHL targeting of HIF-alpha subunits follows hydroxylation of critical HIF prolyl residues by a group of oxygen. 2-oxoglutarate- and iron-dependent enzymes. In this review, we outline current understanding of HIF/pVHL/prolyl hydroxylase pathway and consider the implications for VHL-associated cancer. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：83 / 89

页数：7

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