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Role of Heat Shock Protein 90 in Diabetes and Pancreatic Cancer Management

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Exploring Pancreatic Metabolism and Malignancy

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Abstract

Heat shock protein 90 (Hsp90) plays a key role in the activation of client proteins, which implicate Hsp90 in various biological processes, specifically coordinating regulatory mechanisms in order to control their activity. One of the key regulators responsible for the upregulation of Hsp90 is heat shock factor (HSF1), whose primary role is to bind heat shock elements (HSEs) with Hsp90 promoters. HSF1 functions by interacting with the transcriptional programming of Hsp90 and with integrate biological signals to regulate levels of Hsp90, especially during times of stress. Furthermore, not only are these Hsp90 protein chaperones upregulated but they can also be released from pancreatic beta cells during pro-inflammatory circumstances. Additionally, Hsp90 interferes with survival and metastatic pathways that are associated with pancreatic cancer (PC) progression. Future investigations on protein chaperons that are associated with Hsp90 may lead to the identification of biomarkers for diseases such as diabetes and PCs and potentially lead to therapeutic strategies in management of these chronic diseases.

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Abbreviations

17-DMAG:

17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin

ATP:

Adenosine triphosphate

CTA:

C-terminal transactivation

DBD:

DNA-binding domain

FAK:

Focal adhesion kinase

HIF-1a:

Hypoxia-induced factor-1α

HSEs:

Heat shock elements

HSF:

Heat shock factor

Hsp90:

Heat shock protein 90

HSR:

Heat shock response

IGF-IR:

Insulin-like growth factor-1 receptor

IL-6:

Interleukin-6

NK cells:

Natural killer cells

NTA:

N-terminal transactivation

PBMC:

Peripheral blood mononuclear cell

PC:

Pancreatic cancer

T1D:

Type 1 diabetes

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Biotechnology, Dr. NTR University of Health Sciences, Vijayawada, Andhra Pradesh, India

    Pinninti Santosh Sushma

  2. Department of Bioscience and Biotechnology, Banasthali University, Vanasthali, Rajasthan, India

    Saimila Momin & Gowru Srivani

  3. Department of Biology, Emory University, Atlanta, GA, USA

    Saimila Momin

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  1. Pinninti Santosh Sushma
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  2. Saimila Momin
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  3. Gowru Srivani
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Correspondence to Pinninti Santosh Sushma .

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Editors and Affiliations

  1. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA

    Ganji Purnachandra Nagaraju

  2. Department of Animal Biology, University of Hyderabad, Hyderabad, Telangana, India

    Aramati BM Reddy

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Sushma, P.S., Momin, S., Srivani, G. (2019). Role of Heat Shock Protein 90 in Diabetes and Pancreatic Cancer Management. In: Nagaraju, G., BM Reddy, A. (eds) Exploring Pancreatic Metabolism and Malignancy. Springer, Singapore. https://doi.org/10.1007/978-981-32-9393-9_11

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