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Mol Biol Cell. 2004 Sep;15(9):4003-10. Epub 2004 Jun 23.

The cochaperone HspBP1 inhibits the CHIP ubiquitin ligase and stimulates the maturation of the cystic fibrosis transmembrane conductance regulator.

Author information

1
Institut für Zellbiologie and Bonner Forum Biomedizin, Rheinische Friedrich-Wilhelms-Universität Bonn, D-53121 Bonn, Germany.

Abstract

The CHIP ubiquitin ligase turns molecular chaperones into protein degradation factors. CHIP associates with the chaperones Hsc70 and Hsp90 during the regulation of signaling pathways and during protein quality control, and directs chaperone-bound clients to the proteasome for degradation. Obviously, this destructive activity should be carefully controlled. Here, we identify the cochaperone HspBP1 as an inhibitor of CHIP. HspBP1 attenuates the ubiquitin ligase activity of CHIP when complexed with Hsc70. As a consequence, HspBP1 interferes with the CHIP-induced degradation of immature forms of the cystic fibrosis transmembrane conductance regulator (CFTR) and stimulates CFTR maturation. Our data reveal a novel regulatory mechanism that determines folding and degradation activities of molecular chaperones.

PMID:
15215316
PMCID:
PMC515335
DOI:
10.1091/mbc.e04-04-0293
[Indexed for MEDLINE]
Free PMC Article

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