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
Celljournal_title
Cellauthors
McClellan AJ,Scott MD,Frydman Jdoi
10.1016/j.cell.2005.03.024subject
Has Abstractpub_date
2005-06-03 00:00:00pages
739-48issue
5eissn
0092-8674issn
1097-4172pii
S0092-8674(05)00296-5journal_volume
121pub_type
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