The von Hippel-Lindau tumor suppressor protein: new insights into oxygen sensing and cancer

被引：148

作者：

Kim, W

Kaelin, WG

机构：

[1] Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Boston, MA 02115 USA

来源：

CURRENT OPINION IN GENETICS & DEVELOPMENT | 2003年 / 13卷 / 01期

关键词：

D O I：

10.1016/S0959-437X(02)00010-2

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The von Hippel-Lindau tumor suppressor protein (pVHL) is the substrate-recognition module of an E3 ubiquitin ligase that targets the alpha subunits of hypoxia-inducible factor (HIF) for degradation in the presence of oxygen. Recognition of HIF by pVHL is linked to enzymatic hydroxylation of conserved prolyl residues in the HIF alpha subunits by members of the EGLN family. Dysregulation of HIF-target genes such as vascular endothelial growth factor and transforming growth factor a has been implicated in the pathogenesis of renal cell carcinomas and of hemangioblastomas, both of which frequently lack pVHL function.

引用

页码：55 / 60

页数：6

共 60 条

[1] Rapid and durable recovery of visual function in a patient with von Hippel-Lindau syndrome after systemic therapy with vascular endothelia growth factor receptor inhibitor SU5416
Aiello, LP
George, DJ
Cahill, MT
Wong, JS
Cavallerano, J
Hannah, AL
Kaelin, WG
[J]. OPHTHALMOLOGY, 2002, 109 (09) : 1745 - 1751
[2] Aravind L., 2001, GENOME BIOL, V2, p7.1
[3] Hypoxia-inducible factor-1α (HIF-1α) escapes O2-driven proteasomal degradation irrespective of its subcellular localization:: nucleus or cytoplasm
Berra, E
Roux, D
Richard, DE
Pouysségur, J
[J]. EMBO REPORTS, 2001, 2 (07) : 615 - 620
[4] Bindra RS, 2002, CANCER RES, V62, P3014
[5] A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, RK
McKnight, SL
[J]. SCIENCE, 2001, 294 (5545) : 1337 - 1340
[6] Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease
Clifford, SC
Cockman, ME
Smallwood, AC
Mole, DR
Woodward, ER
Maxwell, PH
Ratcliffe, PJ
Maher, ER
[J]. HUMAN MOLECULAR GENETICS, 2001, 10 (10) : 1029 - 1038
[7] Structural basis for Hif-1α/CBP recognition in the cellular hypoxic response
Dames, SA
Martinez-Yamout, M
De Guzman, RN
Dyson, HJ
Wright, PE
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (08) : 5271 - 5276
[8] Inhibition of insulin-like growth factor-I-mediated cell signaling by the von Hippel-Lindau gene product in renal cancer
Datta, K
Nambudripad, R
Pal, S
Zhou, M
Cohen, HT
Mukhopadhyay, D
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (27) : 20700 - 20706
[9] Datta K, 2001, CANCER RES, V61, P1768
[10] VHL induces renal cell differentiation and growth arrest through integration of cell-cell and cell-extracellular matrix signaling
Davidowitz, EJ
Schoenfeld, AR
Burk, RD
[J]. MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (03) : 865 - 874

← 1 2 3 4 5 6 →