Chaperone functions of the E3 ubiquitin ligase CHIP.
The carboxyl terminus of the Hsc70-interacting protein (CHIP) is an Hsp70 co-chaperone as well as an E3 ubiquitin ligase that protects cells from proteotoxic stress. The abilities of CHIP to interact with Hsp70 and function as a ubiquitin ligase place CHIP at a pivotal position in the protein quality control system, where its entrance into Hsp70-substrate complexes partitions nonnative proteins toward degradation. However, the manner by which Hsp70 substrates are selected for ubiquitination by CHIP is not well understood. We discovered that CHIP possesses an intrinsic chaperone activity that enables it to selectively recognize and bind nonnative proteins. Interestingly, the chaperone function of CHIP is temperature-sensitive and is dramatically enhanced by heat stress. The ability of CHIP to recognize nonnative protein structure may aid in selection of slow folding or misfolded polypeptides for ubiquitination.
Rosser
Meredith F N
MF
Department of Cell and Developmental Biology, University of North Carolina Chapel Hill School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Washburn
Erin
E
Muchowski
Paul J
PJ
Patterson
Cam
C
Cyr
Douglas M
DM
D002460:Cell Line; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006358:Hot Temperature; D006801:Humans; D000071058:Huntingtin Protein; D008156:Luciferases / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry; D009687:Nuclear Proteins / Q000737:chemistry; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry*
D003432:Cross-Linking Reagents; C086055:HTT protein, human; D000071058:Huntingtin Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025801:Ubiquitin; D008156:Luciferases; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases; D013884:Thiosulfate Sulfurtransferase