Regulation of heat shock transcription factors and their roles in physiology and disease
By Rocío Gómez-Pastor, Eileen T. Burchfiel, D. Thiele. Nature reviews. Molecular cell biology, 2017
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The heat shock transcription factors (HSFs) were discovered over 30 years ago as direct transcriptional activators of genes regulated by thermal stress, encoding heat shock proteins. The accepted paradigm posited that HSFs exclusively activate the expression of protein chaperones in response to conditions that cause protein misfolding by recognizing a simple promoter binding site referred to as a heat shock element. However, we now realize that the mammalian family of HSFs comprises proteins that independently or in concert drive combinatorial gene regulation events that activate or repress transcription in different contexts. Advances in our understanding of HSF structure, post-translational modifications and the breadth of HSF-regulated target genes have revealed exciting new mechanisms that modulate HSFs and shed new light on their roles in physiology and pathology. For example, the ability of HSF1 to protect cells from proteotoxicity and cell death is impaired in neurodegenerative diseases but can be exploited by cancer cells to support their growth, survival and metastasis. These new insights into HSF structure, function and regulation should facilitate the development tof new disease therapeutics to manipulate this transcription factor family.
Subfields: Cell Biology, Molecular Biology, Physical and Theoretical Chemistry
View Paper: https://www.semanticscholar.org/paper/28c35e923d5e8b2b7140eb4b9e41d035286b4436
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Citations in the corpus
- Mutant p53 as a guardian of the cancer cell (2018, neutral): “During oncogenic transformation the Hsp90 system is frequently hyper-induced, due to activation of the master transcription factor heat-shock factor-1 (HSF1) in response to multiple stress conditions [14, 15].”
- Pathways of cellular proteostasis in aging and disease (2018, background): “Finally, once the stressor is removed, a negative-feedback loop on Hsf1 activity ensures a return to stasis within the system (Akerfelt et al., 2010; Gomez-Pastor et al., 2017).”