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Hsp90 and Its Role in Heme-Maturation of Client Proteins: Implications for Human Diseases

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Book cover Heat Shock Protein 90 in Human Diseases and Disorders

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

Abstract

Hemeproteins are essential for life and heme insertion is an essential step in their maturation. Maturation of hemeprotein requires that they incorporate heme and become active, but knowledge of this essential cellular process remains incomplete. However recent studies on chaperon Hsp90 has revealed that it drives functional heme insertion in vital hemeproteins like inducible nitric oxide synthase (iNOS), soluble guanylate cyclase (sGC) and hemoglobin (Hb). In all three cases Hsp90 interacts with the heme-free or apo-protein and then drives the heme insertion by an ATP dependent process before dissociating from the heme-replete proteins. Given the diverse role of chaperon Hsp90, and in particular to it being a major therapeutic target in drug discovery programs these findings add up to Hsp90’s repertoire of being a druggable target and opens up more avenues in regulating growth of diseased cells in those pathologic conditions where these hemeproteins are dysfunctional.

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Abbreviations

AHSP:

Alpha hemoglobin stabilizing protein

AIF:

Apoptosis-inducing factor

Apaf-1:

Apoptotic protease activating factor 1

Ask-1:

Apoptosis signal-regulating kinase 1

ATP:

Adenosine triphosphate

cGMP:

Cyclic guanosine monophosphate

ECM:

Extracellular matrix

FLVCRb:

Feline leukemia virus subgroup c receptor b

Hb:

Hemoglobin

HDM:

House dust mite

Her-2:

Human epidermal growth factor receptor 2

Hip:

hsp70-interacting protein

H-NOX:

Heme nitric oxide/oxygen

Hop:

hsp70/hsp90 organizing protein

Hsp90:

Heat shock protein 90

iNOS:

Inducible nitric oxide synthase

IPF:

Idiopathic pulmonary fibrosis

MMPs:

Matrix metalloproteinases

NO:

Nitric oxide

NOS:

Nitric oxide synthase

NOX:

NADPH oxidase

per2:

Period circadian regulator 2

ROS:

Reactive oxygen species

sGC:

Soluble guanylate cyclase

TGF-β1:

Transforming growth factor-β1

VEGF:

Vascular endothelial growth factor

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Acknowledgements

This work is supported by National Institute of Health Grant HL081064 (to D.J.S and A.G.) and a Research Centre for Excellence Grant from the Cleveland Clinic (to A.G. and D.J.S.).

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  1. Department of Inflammation and Immunity, Lerner Research Institute, The Cleveland Clinic, Cleveland, OH, USA

    Arnab Ghosh & Dennis J. Stuehr

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  1. Arnab Ghosh
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Correspondence to Arnab Ghosh .

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  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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Ghosh, A., Stuehr, D.J. (2019). Hsp90 and Its Role in Heme-Maturation of Client Proteins: Implications for Human Diseases. 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_12

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