Scientific Background: HSF1 is a member of the heat shock transcription factor family. Protein-damaging stress lead to the activation of HSF1 which binds to upstream regulatory sequences in the promoters of heat shock genes leading to enhanced heat shock gene expression (1). The activation of HSF1 proceeds through a multi-step pathway, involving a monomer-to-trimer transition, nuclear accumulation and extensive posttranslational modifications. HSF1 activity is regulated at different levels by heat shock proteins and co-chaperones and is modulated further by a number of mechanisms involving other stress-regulated aspects of cell metabolism (2).
2. Voellmy, R.: Feedback regulation of the heat shock response. Handb Exp Pharmacol. 2006;(172):43-68.
NCBI and Uniprot Product Information
NCBI Description
The product of this gene is a heat-shock transcription factor. Transcription of heat-shock genes is rapidly induced after temperature stress. Hsp90, by itself and/or associated with multichaperone complexes, is a major repressor of this gene. [provided by RefSeq, Jul 2008]
Uniprot Description
Function: DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. In higher eukaryotes, HSF is unable to bind to the HSE unless the cells are heat shocked. Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18
Subunit structure: Monomer. Under normal conditions, interacts with HSP90AA1 in the HSP90 multichaperone complex; the interaction prevents trimerization and activation of HSF1. On activation by heat-stress or by other factors such as metal ions, HSF1 is released from the complex, homotrimerizes, is hyperphosphorylated and translocated to the nucleus where, subsequently, it can activate transcription. Binds the complex through the regulatory domain. Interacts with SYMPK and CSTF2 in heat-stressed cells. Interacts with FKBP4 in the HSP90 multichaperone complex; the interaction is independent of the phosphorylation state of HSF1. Interacts with MAPKAPK2. Interacts with EEF1D at heat shock promoter elements (HSE). Ref.13 Ref.16 Ref.18 Ref.26
Subcellular location: Cytoplasm. Nucleus. Note: Cytoplasmic during normal growth. On activation, translocates to nuclear stress granules. Colocalizes with SUMO1 in nuclear stress granules. Ref.7 Ref.15
Domain: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. Ref.8 Ref.20
Post-translational modification: Phosphorylated on multiple serine residues, a subset of which are involved in stress-related regulation of transcription activation. Constitutive phosphorylation represses transcriptional activity at normal temperatures. Levels increase on specific residues heat-shock and enhance HSF1 transactivation activity. Phosphorylation on Ser-307 derepresses activation on heat-stress and in combination with Ser-303 phosphorylation appears to be involved in recovery after heat-stress. Phosphorylated on Ser-230 by CAMK2, in vitro. Cadmium also enhances phosphorylation at this site. Phosphorylation on Ser-303 is a prerequisite for HSF1 sumoylation. Phosphorylation on Ser-121 inhibits transactivation and promotes HSP90 binding. Phosphorylation on Thr-142 also mediates transcriptional activity induced by heat. Ref.7 Ref.9 Ref.10 Ref.11 Ref.13 Ref.14 Ref.15 Ref.18 Ref.19Sumoylated with SUMO1 and SUMO2 on heat-shock. Heat-inducible sumoylation occurs after 15 min of heat-shock, after which levels decrease and at 4 hours, levels return to control levels. Sumoylation has no effect on HSE binding nor on transcriptional activity. Phosphorylation on Ser-303 is a prerequisite for sumoylation. Ref.12 Ref.15 Ref.19
Sequence similarities: Belongs to the HSF family.
Research Articles on HSF1
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Product Notes
The HSF1 hsf1 (Catalog #AAA515437) is a Recombinant Protein produced from E Coli and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||E.coli!!Source Note||Recombinant full length human HSF1 was expressed in E.coli cells. AAA Biotech's HSF1 can be used in a range of immunoassay formats including, but not limited to, Kinase Assay, Western Blot (WB). Researchers should empirically determine the suitability of the HSF1 hsf1 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "HSF1, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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