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Roles of heat shock factor 1 beyond the heat shock response

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Abstract

Various stress factors leading to protein damage induce the activation of an evolutionarily conserved cell protective mechanism, the heat shock response (HSR), to maintain protein homeostasis in virtually all eukaryotic cells. Heat shock factor 1 (HSF1) plays a central role in the HSR. HSF1 was initially known as a transcription factor that upregulates genes encoding heat shock proteins (HSPs), also called molecular chaperones, which assist in refolding or degrading injured intracellular proteins. However, recent accumulating evidence indicates multiple additional functions for HSF1 beyond the activation of HSPs. Here, we present a nearly comprehensive list of non-HSP-related target genes of HSF1 identified so far. Through controlling these targets, HSF1 acts in diverse stress-induced cellular processes and molecular mechanisms, including the endoplasmic reticulum unfolded protein response and ubiquitin–proteasome system, multidrug resistance, autophagy, apoptosis, immune response, cell growth arrest, differentiation underlying developmental diapause, chromatin remodelling, cancer development, and ageing. Hence, HSF1 emerges as a major orchestrator of cellular stress response pathways.

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Acknowledgements

This work was supported by the grants OTKA (Hungarian Scientific Research Fund) NK78012 and K115378, MEDinPROT Protein Science Research Synergy Program (provided by the Hungarian Academy of Sciences; HAS), and VEKOP (VEKOP-2.3.2-16-2017-00014). B.J and T.V. are also supported by the MTA-ELTE Genetics Research Group (01062).

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Each author (JB, PC, and TV) has participated in collecting non-HSP targets of HSF1, characterising the role of HSF1 in functions other than the HSR, and writing the manuscript.

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Correspondence to Tibor Vellai.

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Barna, J., Csermely, P. & Vellai, T. Roles of heat shock factor 1 beyond the heat shock response. Cell. Mol. Life Sci. 75, 2897–2916 (2018). https://doi.org/10.1007/s00018-018-2836-6

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