Folding and Quality Control of the VHL Tumor Suppressor Proceed through Distinct Chaperone Pathways
Date
2005-06
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
The mechanisms by which molecular chaperones assist quality control of cytosolic proteins are poorly understood. Analysis of the chaperone requirements for degradation of misfolded variants of a cytosolic protein, the VHL tumor suppressor, reveals that distinct chaperone pathways mediate its folding and quality control. While both folding and degradation of VHL require Hsp70, the chaperon in TRiC is essential for folding but is dispensable for degradation. Conversely, the chaperone Hsp90 neither participates in VHL folding nor is required to maintain misfolded VHL solubility but is essential for its degradation. The cochaperone HOP/Sti1p also participates in VHL quality control and may direct the triage decision by bridging the Hsp70-Hsp90 interaction. Our finding that a distinct chaperone complex is uniquely required for quality control provides evidence for active and specific chaperone participation in triage decisions and suggests that a hierarchy of chaperone interactions can control the alternate fates of a cytosolic protein.
Description
item.page.type
Article
item.page.format
Keywords
Heat shock proteins -- Analysis, Tumors -- Analysis, Proteins -- Analysis, Quality control -- Analysis
Citation
Cell, Vol. 121, 739–748, June 3, 2005, Copyright ©2005 by Elsevier Inc. DOI 10.1016/j.cell.2005.03.024