Von Hippel-Lindau protein and respiratory diseases

Core Tip

Core tip: Although von Hippel-Lindau protein (pVHL) was first identified as a tumor suppressor and is best known as a component of ubiquitin protein ligase for the proteasomal degradation of hypoxia inducible factor (HIF)-α, recent studies suggest that pVHL contributes to many lung diseases in both HIF-dependent and HIF-independent pathways. Loss of pVHL promotes pulmonary arterial hypertension via activation of HIF. In lung cancer, loss of pVHL promotes epithelial-mesenchymal transition and cancer migration and invasion while decreasing cell proliferation and colonization. pVHL also induces fibronectin/integrin α5β1/focal adhesion kinase signaling to facilitate fibrogenesis. pVHL mediates Na-K-ATPase degradation to cause decreased edema clearance during hypoxia.