Folding and quality control of the VHL tumor suppressor proceed through distinct chaperone pathways.

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 chaperonin 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.

journal_name

Cell

journal_title

Cell

authors

McClellan AJ,Scott MD,Frydman J

doi

10.1016/j.cell.2005.03.024

subject

Has Abstract

pub_date

2005-06-03 00:00:00

pages

739-48

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092-8674(05)00296-5

journal_volume

121

pub_type

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