Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1
By S. Westerheide, J. Anckar, S. Stevens, Lea Sistonen, Richard I. Morimoto. Science, 2009
750 citations recorded by the source corpus.
Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA–binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the regulation of life span and establish a role for SIRT1 in protein homeostasis and the HSR.
Subfields: Aging, Geriatrics and Gerontology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0488f05db75f973077fafc3253c7e183be61701f
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In Aging
In Geriatrics and Gerontology
In Molecular Biology
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- Manuel Serrano
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- M. Haslbeck
- C. López‐Otín
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- J. Buchner
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Citations in the corpus
- The hallmarks of aging. (2013, background): “In mammalian cells, deacetylation of HSF-1 by SIRT1 potentiates the transactivation of heat-shock genes such as Hsp70, whereas down-regulation of SIRT1 attenuates the heat-shock response (Westerheide et al., 2009).”
- Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “4 and 11) (452, 466).”
- The heat shock response: life on the verge of death. (2010, background): “Hsf1 acetylation has recently been reported to downregulate it (Westerheide et al., 2009).”