The Prefoldin Complex Stabilizes the Von Hippel-Lindau Protein Against Aggregation and Degradation

Overview

Journal PLoS Genet

Specialty Genetics

Date 2020 Nov 2

PMID 33137104

Citations 7

Authors

Franck Chesnel

Anne Couturier

Adrien Alusse

Jean-Philippe Gagne

Guy G Poirier

Dominique Jean

Francois-Michel Boisvert

Pauline Hascoet

Luc Paillard

Yannick Arlot-Bonnemains

Xavier Le Goff

Affiliations

Soon will be listed here.

Abstract

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 in Schizosaccharomyces 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 were 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.

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