pVHL 19 is a biologically active product of the von Hippel–Lindau gene arising from internal translation initiation

Abstract

The von Hippel–Lindau (VHL) gene encodes a protein consisting of 213 amino acid residues with an apparent molecular mass of 30 kDa (pVHL 30 ). Here we show that cells also produce a VHL protein (pVHL 19 ) that appears to arise as a result of internal translation from the second methionine within the VHL ORF. pVHL 30 resides primarily in the cytosol, with less amounts found in the nucleus or associated with cell membranes. In contrast pVHL 19 , in biochemical fractionation experiments, is equally distributed between the nucleus and cytosol and is not found in association with membranes. pVHL 19 , like pVHL 30 , can bind to elongin B, elongin C, and Hs-Cul2 in coimmunoprecipitation assays and can inhibit the production of hypoxia-inducible proteins such as vascular endothelial growth factor (VEGF) and GLUT1 when reintroduced into renal carcinoma cells that lack a wild-type VHL allele. Thus, cells contain two biologically active VHL gene products.