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


Autoři: Franck Chesnel aff001;  Anne Couturier aff001;  Adrien Alusse aff001;  Jean-Philippe Gagné aff002;  Guy G. Poirier aff002;  Dominique Jean aff004;  François-Michel Boisvert aff004;  Pauline Hascoet aff001;  Luc Paillard aff001;  Yannick Arlot-Bonnemains aff001;  Xavier Le Goff aff001
Působiště autorů: Univ Rennes, CNRS, IGDR (Institut de génétique et développement de Rennes)—UMR 6290, France aff001;  Department of Molecular Biology, Medical Biochemistry and Pathology; Université Laval, Québec City, Québec, Canada aff002;  CHU de Québec Research Center, CHUL Pavilion, Oncology Axis, Québec City, Québec, Canada aff003;  Department of Anatomy and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada aff004
Vyšlo v časopise: The prefoldin complex stabilizes the von Hippel-Lindau protein against aggregation and degradation. PLoS Genet 16(11): e32767. doi:10.1371/journal.pgen.1009183
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009183

Souhrn

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.

Klíčová slova:

Fluorescence imaging – HeLa cells – Phenotypes – Protein extraction – Protein folding – Schizosaccharomyces pombe – Small interfering RNA – Yeast


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