VHL and HIF in Clear Cell Renal Cell Carcinoma: Molecular Abnormalities and Potential Clinical Applications

摘要: Biallelic inactivation of the von Hippel-Lindau (VHL) gene occurs in majority sporadic clear cell renal carcinomas (ccRCCs) due to a combination somatic mutations, VHL promoter methylation and loss heterozygosity by allele deletion. The most well-documented function pVHL relates its role as substrate-recognition component VHL-elongin C-elongin B-cullin 2-Rbx1 E3 ubiquitin ligase complex. This complex is best known for ability target hypoxia-inducible factors (HIFs) polyubiquitination proteasomal degradation. HIFs play critical cellular adaptation reduced oxygen tension. Three HIFα family members (HIF1α, HIF2α HIF3α) two HIFβ (HIF1β HIF2β) have been described. balance evidence suggests that ccRCC, HIF1α acts tumour suppressor, while oncoprotein. also has HIF-independent functions though these are less well characterised. In this chapter, we examine detail protein alongside main downstream target, factor (HIF). results from several studies which investigated whether mutational status or expression useful biomarker ccRCC reviewed.