Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation.

Inhibition of FIH under hypoxic conditions facilitates CBP/p300 recruitment, resulting in increased HIF target gene expression in VHL-deficient cell lines or under pronounced hypoxia [42–45]. Certain mutations in the VHL gene result in the development of familial polycythemia from excessive EPO production [ 46 ], but not in tumorigenesis.

May 20, 1999 · Here we demonstrate a critical role for the von Hippel-Lindau (VHL) tumour suppressor gene product pVHL in HIF-1 regulation. In VHL-defective cells, HIF α-subunits are constitutively stabilized...

Dec 23, 2014 · VHL tumour suppressor protein (pVHL) plays a key part in cellular oxygen sensing by targeting hypoxia-inducible factors for ubiquitylation and proteasomal degradation.

Mar 19, 2018 · Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation.

Aug 14, 2001 · Under normoxic conditions, HIF-1α is recognized by the von Hippel-Lindau tumor-suppressor protein (VHL), a component of an E3 ubiquitin ligase complex. This interaction thereby promotes the rapid degradation of HIF-1α. Under hypoxic conditions, HIF-1α is stabilized.

Gene expression analysis was performed on a human renal cancer cell line (786-0) with mutated VHL gene and a transfectant with wild-type VHL to analyse genes regulated by VHL and to compare with the gene programme regulated by hypoxia.

Jan 25, 2008 · Germ-line mutations in the von Hippel–Lindau tumor (VHL) suppressor can be found in patients with VHL disease, a rare familial tumor syndrome characterized by the development of highly...

During hypoxia, the proline residues are not hydroxylated and pVHL cannot bind. HIF1α causes the transcription of genes that contain the hypoxia response element. In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site.

Nov 24, 2021 · Patients with von Hippel–Lindau (VHL) disease have a high incidence of renal cell carcinoma owing to VHL gene inactivation and constitutive activation of the transcription factor...