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HSP90 et al.: Chaperome and Proteostasis Deregulation in Human Disease

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Heat Shock Protein 90 in Human Diseases and Disorders

Part of the book series: Heat Shock Proteins ((HESP,volume 19))

Abstract

HSP90 action as a conserved chaperone is fundamental to the folding and maturation of a large fraction of structurally and functionally diverse proteins. Through its wide spectrum of clients and their connectivity within the proteome, HSP90 is a key factor in the processes that maintain cellular proteostasis, referred to as the proteostasis network (PN). Besides HSP90, hundreds of additional molecular chaperones and co-chaperones act together in complexes and intricate networks to maintain the cellular native folding environment, avoid misfolding, and redirect non-native folding intermediates back to their native state or towards clearance. The ensemble of all cellular chaperones and co-chaperones constitute the chaperome, which acts to regulate and maintain proteome functionality. Recent insights derived from systematic studies have revealed vast imbalances to cellular proteostasis reflected by chaperome deregulation from aging, to neurodegenerative diseases, and cancers. Deregulation states along with specific chaperome connectivity can represent biomarkers for certain diseases. HSP90 is not acting in isolation but as a component of a comprehensive and dynamic chaperome interactome network. Therefore, a detailed understanding of systems-level alterations of chaperome biology is fundamental towards a better understanding of HSP90 action and its therapeutic targeting in health and disease.

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Abbreviations

HSP:

Heat shock protein

HSP90:

Heat shock protein 90

PN:

Proteostasis network

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Acknowledgements

The authors would like to acknowledge Richard Morimoto, Marc Vidal, Andreas Schuppert, Julio Saez-Rodriguez, Angelina Sverchkova, and Ali Hadizadeh-Esfahani for their support and contributions to the authors’ research referenced in this chapter. Figure 27.1 reproduced from Brehme and Voisine, Disease Models & Mechanisms (2016) 9, 823–838, https://doi.org/10.1242/dmm.024703 with permission of Disease Models & Mechanisms.

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Authors and Affiliations

  1. Department of Biology, Northeastern Illinois University, Chicago, IL, USA

    Cindy Voisine

  2. CB - med Center for Biomarker Research in Medicine GmbH, Graz, Austria

    Marc Brehme

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  1. Cindy Voisine
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  2. Marc Brehme
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Correspondence to Marc Brehme .

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Editors and Affiliations

  1. Department of Medicine and Director, Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo, College of Medicine and Life Sciences, Toledo, OH, USA

    Alexzander A. A. Asea

  2. Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Voisine, C., Brehme, M. (2019). HSP90 et al.: Chaperome and Proteostasis Deregulation in Human Disease. In: Asea, A., Kaur, P. (eds) Heat Shock Protein 90 in Human Diseases and Disorders. Heat Shock Proteins, vol 19. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_27

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