Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin

Dhanani, Karim C H; Samson, William J; Edkins, Adrienne L

Title: Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin
Creator: Dhanani, Karim C H, Samson, William J, Edkins, Adrienne L
Date: 2017
Type: article
Type: text
Identifier: http://hdl.handle.net/10962/59931
Identifier: vital:27711
Identifier: https://doi:10.1038/s41598-017-18061-y
Description: Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels. Geldanamycin treatment induced a stress response and a strong dose and time dependent increase in fibronectin mRNA via activation of the fibronectin promoter. Three putative heat shock elements (HSEs) were identified in the fibronectin promoter. Loss of two of these HSEs reduced both basal and geldanamycin-induced promoter activity, as did inhibition of the stress-responsive transcription factor HSF1. Binding of HSF1 to one of the putative HSE was confirmed by ChIP under basal conditions, and occupancy shown to increase with geldanamycin treatment. These data support the hypothesis that fibronectin is stress-responsive and a functional HSF1 target gene. COLA42 and LAMB3 mRNA levels were also increased with geldanamycin indicating that regulation of extracellular matrix (ECM) genes by HSF1 may be a wider phenomenon. Taken together, these data have implications for our understanding of ECM dynamics in stress-related diseases in which HSF1 is activated, and where the clinical application of N-terminal Hsp90 inhibitors is intended.
Format: 13 pages, pdf
Language: English
Relation: Scientific Reports, Dhanani, K.C.H., Samson, W.J. and Edkins, A.L., 2017. Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin. Scientific reports, 7(1), p.17617, Scientific Reports 7 vol. 1 no. 1 13 2017 2045-2322
Rights: Scientific Report
Rights: Use of this resource is governed by the terms and conditions of the Scientific Reports Open Access Policy

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RU DST/NRF SARChI for Molecular and Cellular Biology of the Eukaryotic Stress Response

Edkins, Adrienne Lesley (Associate Prof)

SDG 03. Good Health and Well-Being

RU Department of Biochemistry, Microbiology and Bioinformatics

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