Disease relevance of Vhl

• Thus, loss of pVHL function may be causative in pheochromocytoma-associated hypercatecholaminemia and arterial hypertension [1].
• A decrease in pVHL accumulation also resulted in an increase in TH mRNA accumulation and transcription of the TH gene during hypoxia [1].
• It has been shown that pVHL can suppress the expression of certain genes that are overexpressed in renal carcinomas [2].

High impact information on Vhl

• PC12 cells that express VHL antisense RNA had 5-10-fold reduced levels of endogenous pVHL and 2-3-fold increased levels of TH protein and mRNA [1].
• This is the first evidence that endogenous pVHL is a physiological regulator of the catecholaminergic phenotype [1].
• In addition, neural progenitor cells expressing pVHL following gene transfer showed distinct neuronal differentiation and no induction of HIF-1alpha under the normoxic condition but not under the anoxic condition [3].
• Transient transfection analysis utilizing PDGF-B promoter-chloramphenicol acetyl transferase (CAT) reporter constructs revealed that pVHL inhibition of PDGF-B expression is mediated via the Sp1-binding element in the proximal region of the PDGF-B promoter [2].
• Further analysis of the HIF-alpha degradation regulation revealed that prolyl 4-hydroxylase (P4ha1) and von Hippel-Lindau syndrome homolog (Vhl) were both up-regulated at the troughs compared with the peaks [4].

Other interactions of Vhl

• We also show that some of the effects of pVHL on activity of the TH promoter are mediated through HIFs [5].

References