VHL, the story of a tumour suppressor gene

被引：588

作者：

Gossage, Lucy ^{[1
,2
,3
]}

Eisen, Tim ^{[1
,2
]}

Maher, Eamonn R. ^{[1
,4
,5
]}

机构：

[1] Cambridge Univ Hosp NHS Fdn Trust, Cambridge CB2 0QQ, England

[2] Univ Cambridge, Dept Oncol, Cambridge CB2 0QQ, England

[3] Univ Cambridge, Li Ka Shing Ctr, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[4] Univ Cambridge, Dept Med Genet, Cambridge CB2 0QQ, England

[5] NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

来源：

NATURE REVIEWS CANCER | 2015年 / 15卷 / 01期

基金：

欧洲研究理事会;

关键词：

RENAL-CELL-CARCINOMA; HYPOXIA-INDUCIBLE-FACTOR; HIPPEL-LINDAU-DISEASE; ENDOTHELIAL GROWTH-FACTOR; GENOTYPE-PHENOTYPE CORRELATIONS; BIOLOGICALLY-ACTIVE PRODUCT; GERM-LINE MUTATIONS; RNA-POLYMERASE-II; HIF-ALPHA; MESSENGER-RNA;

D O I：

10.1038/nrc3844

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Since the Von Hippel-Lindau (VHL) disease tumour suppressor gene VHL was identified in 1993 as the genetic basis for a rare disorder, it has proved to be of wide medical and scientific interest. VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation. Early inactivation of VHL is commonly seen in clear-cell renal cell carcinoma (ccRCC), and insights gained from the functional analysis of pVHL have provided the foundation for the routine treatment of advanced-stage ccRCC with novel targeted therapies. However, recent sequencing studies have identified additional driver genes that are involved in the pathogenesis of ccRCC. As our understanding of the importance of VHL matures, it is timely to review progress from its initial description to current knowledge of VHL biology, as well as future prospects for novel medical treatments for VHL disease and ccRCC.

引用

页码：55 / 64

页数：10

共 221 条

[111] Collagen matrix assembly is driven by the interaction of von Hippel-Lindau tumor suppressor protein with hydroxylated collagen IV alpha 2 [J].

Kurban, G. ;

Duplan, E. ;

Ramlal, N. ;

Hudon, V. ;

Sado, Y. ;

Ninomiya, Y. ;

Pause, A. .

ONCOGENE, 2008, 27 (07) :1004-1012

[112] Characterization of a von Hippel Lindau pathway involved in extracellular matrix remodeling, cell invasion, and angiogenesis [J].

Kurban, G ;

Hudon, V ;

Duplan, E ;

Ohh, N ;

Pause, A .

CANCER RESEARCH, 2006, 66 (03) :1313-1319

[113] von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination [J].

Kuznetsova, AV ;

Meller, J ;

Schnell, PO ;

Nash, JA ;

Ignacak, ML ;

Sanchez, Y ;

Conaway, JW ;

Conaway, RC ;

Czyzyk-Krzeska, MF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2706-2711

[114] Novel homozygous VHL mutation in exon 2 is associated with congenital polycythemia but not with cancer [J].

Lanikova, Lucie ;

Lorenzo, Felipe ;

Yang, Chunzhang ;

Vankayalapati, Hari ;

Drachtman, Richard ;

Divoky, Vladimir ;

Prchal, Josef T. .

BLOOD, 2013, 121 (19) :3918-3924

[115] IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE [J].

LATIF, F ;

TORY, K ;

GNARRA, J ;

YAO, M ;

DUH, FM ;

ORCUTT, ML ;

STACKHOUSE, T ;

KUZMIN, I ;

MODI, W ;

GEIL, L ;

SCHMIDT, L ;

ZHOU, FW ;

LI, H ;

WEI, MH ;

CHEN, F ;

GLENN, G ;

CHOYKE, P ;

WALTHER, MM ;

WENG, YK ;

DUAN, DSR ;

DEAN, M ;

GLAVAC, D ;

RICHARDS, FM ;

CROSSEY, PA ;

FERGUSONSMITH, MA ;

LEPASLIER, D ;

CHUMAKOV, I ;

COHEN, D ;

CHINAULT, AC ;

MAHER, ER ;

LINEHAN, WM ;

ZBAR, B ;

LERMAN, MI .

SCIENCE, 1993, 260 (5112) :1317-1320

[116] RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization (Retracted Article) [J].

Lee, KangAe ;

Zhang, Huafeng ;

Qian, David Z. ;

Rey, Sergio ;

Liu, Jun O. ;

Semenza, Gregg L. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (42) :17910-17915

[117] Neuronal apoptosis linked to EgIN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer [J].

Lee, S ;

Nakamura, E ;

Yang, HF ;

Wei, WY ;

Linggi, MS ;

Sajan, MP ;

Farese, RV ;

Freeman, RS ;

Carter, BD ;

Kaelin, WG ;

Schlisio, S .

CANCER CELL, 2005, 8 (02) :155-167

[118] Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations [J].

Li, Lianjie ;

Zhang, Liang ;

Zhang, Xiaoping ;

Yan, Qin ;

Minamishima, Yoji Andrew ;

Olumi, Aria F. ;

Mao, Mao ;

Bartz, Steven ;

Kaelin, William G., Jr. .

MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (15) :5381-5392

[119]

LINDAU ARVID, 1927, ACTA OPHTHALMOL, V4, P193

[120] The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity [J].

Lisztwan, J ;

Imbert, G ;

Wirbelauer, C ;

Gstaiger, M ;

Krek, W .

GENES & DEVELOPMENT, 1999, 13 (14) :1822-1833

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