DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells

Benderska N, Ivanovska J, Rau T, Schulze-Luehrmann J, Mohan S, Chakilam S, Gandesiri M, Ziesche E, Fischer T, Söder S, Agaimy A, Distel L, Sticht H, Mahadevan V, Schneider-Stock R (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Publisher: Company of Biologists

Book Volume: 127

Pages Range: 5273-87

Journal Issue: 24

DOI: 10.1242/jcs.157024

Abstract

Death-associated protein kinase (DAPK) is a serine-threonine kinase with tumor suppressor function. Previously, we demonstrated that tumor necrosis factor (TNF) induced DAPK-mediated apoptosis in colorectal cancer. However, the protein-protein interaction network associated with TNF-DAPK signaling still remains unclear. We identified HSF1 as a new DAPK phosphorylation target in response to low concentrations of TNF and verified a physical interaction between DAPK and HSF1 both in vitro and in vivo. We show that HSF1 binds to the DAPK promoter. Transient overexpression of HSF1 protein led to an increase in DAPK mRNA level and consequently to an increase in the amount of apoptosis. By contrast, treatment with a DAPK-specific inhibitor as well as DAPK knockdown abolished the phosphorylation of HSF1 at Ser230 (pHSF1(Ser230)). Furthermore, translational studies demonstrated a positive correlation between DAPK and pHSF1(Ser230) protein expression in human colorectal carcinoma tissues. Taken together, our data define a novel link between DAPK and HSF1 and highlight a positive-feedback loop in DAPK regulation under mild inflammatory stress conditions in colorectal tumors. For the first time, we show that under TNF the pro-survival HSF1 protein can be redirected to a pro-apoptotic program.

Authors with CRIS profile

Involved external institutions

Shanmugha Arts, Science, Technology & Research Academy (SASTRA University) India (IN) Otto-von-Guericke-Universität Magdeburg Germany (DE)

How to cite

APA:

Benderska, N., Ivanovska, J., Rau, T., Schulze-Luehrmann, J., Mohan, S., Chakilam, S.,... Schneider-Stock, R. (2014). DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells. Journal of Cell Science, 127(24), 5273-87. https://doi.org/10.1242/jcs.157024

MLA:

Benderska, Natalya, et al. "DAPK-HSF1 interaction as a positive-feedback mechanism stimulating TNF-induced apoptosis in colorectal cancer cells." Journal of Cell Science 127.24 (2014): 5273-87.

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