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CHIP: A Co-chaperone for Degradation by the Proteasome

  • Adrienne L. Edkins
Part of the Subcellular Biochemistry book series (SCBI, volume 78)

Abstract

Protein homeostasis relies on a balance between protein folding and protein degradation. Molecular chaperones like Hsp70 and Hsp90 fulfil well-defined roles in protein folding and conformational stability via ATP dependent reaction cycles. These folding cycles are controlled by associations with a cohort of non-client protein co-chaperones, such as Hop, p23 and Aha1. Pro-folding co-chaperones facilitate the transit of the client protein through the chaperone mediated folding process. However, chaperones are also involved in ubiquitin-mediated proteasomal degradation of client proteins. Similar to folding complexes, the ability of chaperones to mediate protein degradation is regulated by co-chaperones, such as the C terminal Hsp70 binding protein (CHIP). CHIP binds to Hsp70 and Hsp90 chaperones through its tetratricopeptide repeat (TPR) domain and functions as an E3 ubiquitin ligase using a modified RING finger domain (U-box). This unique combination of domains effectively allows CHIP to network chaperone complexes to the ubiquitin-proteasome system. This chapter reviews the current understanding of CHIP as a co-chaperone that switches Hsp70/Hsp90 chaperone complexes from protein folding to protein degradation.

Keywords

CHIP STUB1 Ubiquitin Proteasome 

Notes

Acknowledgments

Financial support for research activities in the laboratory of the author from the South African National Research Foundation (NRF), Medical Research Council (MRC) South Africa, Rhodes University and Cancer Association of South Africa (CANSA) is gratefully acknowledged. The views reflected in this document are those of the author and should in no way be attributed to the NRF, MRC, Rhodes University or CANSA.

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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Biochemistry and Microbiology, Biomedical Biotechnology Research Unit (BioBRU)Rhodes UniversityGrahamstownSouth Africa

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