The role of von Hippel-Lindau tumor suppressor protein and hypoxia in renal clear cell carcinoma

被引：48
作者：
Sufan, RI
Jewett, MAS
Ohh, M [1 ]
机构：
[1] Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Dept Urol Surg, Toronto, ON M5G 2M9, Canada
[3] Univ Toronto, Dept Surg Oncol, Toronto, ON M5G 2M9, Canada
[4] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada
来源：
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY | 2004年 / 287卷 / 01期
关键词：
hypoxia-inducible factor; renal cell carcinoma; E3 ubiquitin ligase;
D O I：
10.1152/ajprenal.00424.2003
中图分类号：
Q4 [生理学];
学科分类号：
071003 ;
摘要：
The majority of kidney cancers are caused by the mutation of the von Hippel-Lindau (VHL) tumor suppressor gene. VHL protein (pVHL) is part of an E3 ubiquitin ligase complex called VEC that is composed of elongin B, elongin C, cullin 2, NEDD8, and Rbx1. VEC targets a hypoxia-inducible factor (HIF) transcription factor for ubiquitin-mediated destruction selectively in the presence of oxygen. In the absence of wild-type pVHL, as in VHL patients or in the majority of sporadic clear cell renal cell carcinomas, HIF-responsive genes are inappropriately activated even under normoxia. Recent insights into the molecular mechanisms regulating the function of pVHL, and thereby HIF, in the context of kidney cancer are the focus of this review.
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收藏
页码：F1 / F6
页数：6
相关论文
共 91 条
[1]   SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box [J].
Bai, C ;
Sen, P ;
Hofmann, K ;
Ma, L ;
Goebl, M ;
Harper, JW ;
Elledge, SJ .
CELL, 1996, 86 (02) :263-274
[2]  
Bindra RS, 2002, CANCER RES, V62, P3014
[3]   Alternate choice of initiation codon produces a biologically active product of the von Hippel Lindau gene with tumor suppressor activity [J].
Blankenship, C ;
Naglich, JG ;
Whaley, JM ;
Seizinger, B ;
Kley, N .
ONCOGENE, 1999, 18 (08) :1529-1535
[4]   Oxygen sensing and molecular adaptation to hypoxia [J].
Bunn, HF ;
Poyton, RO .
PHYSIOLOGICAL REVIEWS, 1996, 76 (03) :839-885
[5]   GERMLINE MUTATIONS IN THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE - CORRELATIONS WITH PHENOTYPE [J].
CHEN, F ;
KISHIDA, T ;
YAO, M ;
HUSTAD, T ;
GLAVAC, D ;
DEAN, M ;
GNARRA, JR ;
ORCUTT, ML ;
DUH, FM ;
GLENN, G ;
GREEN, J ;
HSIA, YE ;
LAMIELL, J ;
LI, H ;
WEI, MH ;
SCHMIDT, L ;
TORY, K ;
KUZMIN, I ;
STACKHOUSE, T ;
LATIF, F ;
LINEHAN, WM ;
LERMAN, M ;
ZBAR, B .
HUMAN MUTATION, 1995, 5 (01) :66-75
[6]   Contrasting effects on HIF-1α regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel-Lindau disease [J].
Clifford, SC ;
Cockman, ME ;
Smallwood, AC ;
Mole, DR ;
Woodward, ER ;
Maxwell, PH ;
Ratcliffe, PJ ;
Maher, ER .
HUMAN MOLECULAR GENETICS, 2001, 10 (10) :1029-1038
[7]   Hypoxia inducible factor-α binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein [J].
Cockman, ME ;
Masson, N ;
Mole, DR ;
Jaakkola, P ;
Chang, GW ;
Clifford, SC ;
Maher, ER ;
Pugh, CW ;
Ratcliffe, PJ ;
Maxwell, PH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (33) :25733-25741
[8]   HEREDITARY RENAL-CELL CARCINOMA ASSOCIATED WITH A CHROMOSOMAL TRANSLOCATION [J].
COHEN, AJ ;
LI, FP ;
BERG, S ;
MARCHETTO, DJ ;
TSAI, S ;
JACOBS, SC ;
BROWN, RS .
NEW ENGLAND JOURNAL OF MEDICINE, 1979, 301 (11) :592-595
[9]   Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues [J].
Corless, CL ;
Kibel, AS ;
Iliopoulos, O ;
Kaelin, WG .
HUMAN PATHOLOGY, 1997, 28 (04) :459-464
[10]  
CROSSEY PA, 1994, HUM MOL GENET, V3, P1303
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