title: Regulation of the mammalian heat shock factor 1.
abstract: Living organisms are endowed with the capability to tackle various forms of cellular stress due to the presence of molecular chaperone machinery complexes that are ubiquitous throughout the cell. During conditions of proteotoxic stress, the transcription factor heat shock factor 1 (HSF1) mediates the elevation of heat shock proteins, which are crucial components of the chaperone complex machinery and function to ameliorate protein misfolding and aggregation and restore protein homeostasis. In addition, HSF1 orchestrates a versatile transcriptional programme that includes genes involved in repair and clearance of damaged macromolecules and maintenance of cell structure and metabolism, and provides protection against a broad range of cellular stress mediators, beyond heat shock. Here, we discuss the structure and function of the mammalian HSF1 and its regulation by post-translational modifications (phosphorylation, sumoylation and acetylation), proteasomal degradation, and small-molecule activators and inhibitors.
authors.affiliation: Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, University of Dundee, UK.
authors.forename: Sharadha
authors.initials: S
authors.lastname: Dayalan Naidu
authors.affiliation: Division of Cancer Research, School of Medicine, Jacqui Wood Cancer Centre, University of Dundee, UK.|Department of Pharmacology and Molecular Sciences, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Albena T
authors.initials: AT
authors.lastname: Dinkova-Kostova
mesh_terms: D000107:Acetylation; D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004268:DNA-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D008322:Mammals / Q000235:genetics / Q000502:physiology*; D008958:Models, Molecular; D010766:Phosphorylation; D010802:Phylogeny; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology*; D058207:Sumoylation; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex
keywords: HSF1 activator; HSF1 inhibitor; cytoprotection; hormesis; phytochemical; sulfhydryl reactivity