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CHIP: A Co-chaperone for Degradation by the Proteasome

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The Networking of Chaperones by Co-chaperones

Part of the book series: Subcellular Biochemistry ((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.

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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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  1. Department of Biochemistry and Microbiology, Biomedical Biotechnology Research Unit (BioBRU), Rhodes University, 6140, Grahamstown, South Africa

    Adrienne L. Edkins

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  1. Victoria University, College of Health and Biomedicine, Melbourne, Victoria, Australia

    Gregory Lloyd Blatch

  2. Department of Biochemistry and Microbiology, Rhodes University, Biomedical Biotechnology Research Unit, Grahamstown, South Africa

    Adrienne Lesley Edkins

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Edkins, A. (2015). CHIP: A Co-chaperone for Degradation by the Proteasome. In: Blatch, G., Edkins, A. (eds) The Networking of Chaperones by Co-chaperones. Subcellular Biochemistry, vol 78. Springer, Cham. https://doi.org/10.1007/978-3-319-11731-7_11

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