The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation

by Franck Chesnel, Anne Couturier, Adrien Alusse, Jean-Philippe Gagn é, Guy G. Poirier, Dominique Jean, François-Michel Boisvert, Pauline Hascoet, Luc Paillard, Yannick Arlot-Bonnemains, Xavier Le Goff Loss of von Hippel-Lindau protein pVHL function promotes VHL diseases, including sporadic and inherited clear cell Renal Cell Carcinoma (ccRCC). Mechanisms controlling pVHL function and regulation, including folding and stability, remain elusive. Here, we have identified the conserved cochaperone prefoldin complex in a screen for pVHL interactors. The prefoldin complex delivers non-native proteins to the chaperonin T-complex-protein-1-ring (TRiC) or Cytosolic Chaperonin containing TCP-1 (CCT) to assist folding of newly synthesized polypeptides. The pVHL-prefoldin interaction was confirmed in human cells and prefoldin knock-down reduced pVHL expression levels. Furthermore, when pVHL was expressed inSchizosaccharomyces pombe, all prefoldin mutants promoted its aggregation. We mapped the interaction of prefoldin with pVHL at the exon2-exon3 junction encoded region. Low levels of the PFDN3 prefoldin subunit was associated with poor survival in ccRCC patients harboring VHL mutations. Our results link the prefoldin complex with pVHL folding and this may impact VHL diseases progression.
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research