VHL, the story of a tumour suppressor gene

被引：680

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 [肿瘤学];

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

[1]

VHL expression in renal cell carcinoma sensitizes to bortezomib (PS-341) through an NF-κB-dependent mechanism [J].

An, JB ;

Fisher, M ;

Rettig, MB .

ONCOGENE, 2005, 24 (09) :1563-1570

[2]

Inhibitors of transcription, proteasome inhibitors, and DNA-damaging drugs differentially affect feedback of p53 degradation [J].

An, WG ;

Chuman, Y ;

Fojo, T ;

Blagosklonny, MV .

EXPERIMENTAL CELL RESEARCH, 1998, 244 (01) :54-60

[3]

Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia [J].

Ang, SO ;

Chen, H ;

Hirota, K ;

Gordeuk, VR ;

Jelinek, J ;

Guan, YL ;

Liu, EL ;

Sergueeva, AI ;

Miasnikova, GY ;

Mole, D ;

Maxwell, PH ;

Stockton, DW ;

Semenza, GL ;

Prchal, JT .

NATURE GENETICS, 2002, 32 (04) :614-621

[4]

Loss of von Hippel-Lindau protein causes cell density dependent deregulation of CyclinD1 expression through Hypoxia-inducible factor [J].

Baba, M ;

Hirai, S ;

Yamada-Okabe, H ;

Hamada, K ;

Tabuchi, H ;

Kobayashi, K ;

Kondo, K ;

Yoshida, M ;

Yamashita, A ;

Kishida, T ;

Nakaigawa, N ;

Nagashima, Y ;

Kubota, Y ;

Yao, M ;

Ohno, S .

ONCOGENE, 2003, 22 (18) :2728-2738

[5]

Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases [J].

Bento, Celeste ;

Percy, Melanie J. ;

Gardie, Betty ;

Magalhaes Maia, Tabita ;

van Wijk, Richard ;

Perrotta, Silverio ;

Della Ragione, Fulvio ;

Almeida, Helena ;

Rossi, Cedric ;

Girodon, Francois ;

Astrom, Maria ;

Neumann, Drorit ;

Schnittger, Susanne ;

Landin, Britta ;

Minkov, Milen ;

Randi, Maria Luigia ;

Richard, Stephane ;

Casadevall, Nicole ;

Vainchenker, William ;

Rives, Susana ;

Hermouet, Sylvie ;

Ribeiro, M. Leticia ;

McMullin, Mary Frances ;

Cario, Holger .

HUMAN MUTATION, 2014, 35 (01) :15-26

[6]

Molecular study of congenital erythrocytosis in 70 unrelated patients revealed a potential causal mutation in less than half of the cases (Where is/are the missing gene(s)?) [J].

Bento, Celeste ;

Almeida, Helena ;

Maia, Tabita M. ;

Relvas, Luis ;

Oliveira, Ana C. ;

Rossi, Cedric ;

Girodon, Francois ;

Fernandez-Lago, Carlos ;

Aguado-Diaz, Ascension ;

Fraga, Cristina ;

Costa, Ricardo M. ;

Araujo, Ana L. ;

Silva, Joao ;

Vitoria, Helena ;

Miguel, Natalina ;

Silveira, Maria Pedro ;

Martin-Nunez, Guillermo ;

Ribeiro, Maria Leticia .

EUROPEAN JOURNAL OF HAEMATOLOGY, 2013, 91 (04) :361-368

[7]

Software and database for the analysis of mutations in the VHL gene [J].

Béroud, C ;

Joly, D ;

Gallou, C ;

Staroz, F ;

Orfanelli, MT ;

Junien, C .

NUCLEIC ACIDS RESEARCH, 1998, 26 (01) :256-258

[8]

The Histone Demethylases JMJD1A and JMJD2B Are Transcriptional Targets of Hypoxia-inducible Factor HIF [J].

Beyer, Sophie ;

Kristensen, Malene Maag ;

Jensen, Kim Steen ;

Johansen, Jens Vilstrup ;

Staller, Peter .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (52) :36542-36552

[9]

Bindra RS, 2002, CANCER RES, V62, P3014

[10]

Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans [J].

Bishop, T ;

Lau, KW ;

Epstein, ACR ;

Kim, SK ;

Min, J ;

O'Rourke, D ;

Pugh, CW ;

Gleadle, JM ;

Taylor, MS ;

Hodgkin, J ;

Ratcliffe, PJ .

PLOS BIOLOGY, 2004, 2 (10) :1549-1560

← 1 2 3 4 5 6 7 8 9 10 →