Work

Chaperone Functions of the E3 Ubiquitin Ligase CHIP

Year: 2007

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m700513200

Authors: Meredith F.N. Rosser, Erin Washburn, Paul J. Muchowski, Cam Patterson, Douglas M. Cyr

Institutions: University of North Carolina at Chapel Hill, University of California, San Francisco

Language: Dutch

Topic: Heat shock proteins research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke