Role of the VHL (von Hippel-Lindau) gene in renal cancer:: a multifunctional tumour suppressor

被引：59

作者：

Nyhan, Michelle J. ^{[1
]}

O'Sullivan, Gerald C. ^{[2
]}

McKenna, Sharon L. ^{[1
]}

机构：

[1] Natl Univ Ireland Univ Coll Cork, Leslie C Quick Lab, Cork Canc Res Ctr, Cork, Ireland

[2] Mercy Univ Hosp, Cork, Ireland

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2008年 / 36卷

关键词：

clear-cell renal cell carcinoma; hypoxia-inducible factor (HIF); renal cancer; tumour suppressor; von Hippel-Lindau (VHL); von Hippel-Lindau protein (pVHL);

D O I：

10.1042/BST0360472

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The VHL (von Hippel-Lindau) tumour-suppressor gene is inactivated in VHL disease and in sporadic cases of CCRCC [clear-cell RCC (renal cell carcinoma)]. pVHL (VHL protein) functions as part of an E3 ubiquitin ligase complex that targets proteins for proteasomal degradation. The best-characterized substrate is HIF-alpha (hypoxia-inducible factor-a). Loss of pVHL and subsequent up-regulation of HIF target genes has been attributed to the highly vascular nature of these neoplasms. However, pVHL does not just function as the executioner of HIF-alpha. Additional functions of pVHL that may be important in preventing CCRCC tumorigenesis have been identified, including primary cilium maintenance, assembly of the extracellular matrix and roles in the stabilization of p53 and Jade-1 (gene for apoptosis and differentiation in epithelia). Current evidence indicates that pVHL probably requires additional co-operating signalling pathways for CCRCC initiation and tumorigenesis.

引用

页码：472 / 478

页数：7

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