Pathway
HSF1-dependent transactivation
Acquisition of DNA binding activity by HSF1 is necessary but insufficient for transcriptional activation (Cotto JJ et al. 1996; Trinklein ND et al. 2004). In addition to having a sequence-specific DNA binding domain, HSF1 contains a C-terminal region which is involved in activating the transcription of the target genes (Green M et al. 1995). However, the transactivating ability of the transactivation domain itself is not stress sensitive. Rather, it's controled by a regulatory domain of HSF1 (amino acids 221-310), which represses the transactivating ability under normal physiological conditions (Green M et al. 1995; Zuo J et al. 1995; Newton EM et al. 1996). The HSF1 transactivation domain can be divided into two distinct regions, activation domain 1 (AD1) and activation domain 2 (AD2) (Brown SA et al. 1998). AD1 and AD2 each contain residues that are important for both transcriptional initiation and elongation. Mutations in acidic residues in both AD1 and AD2 preferentially affect the ability of HSF1 to stimulate transcriptional initiation, while mutations in phenylalanine residues preferentially affect stimulation of elongation (Brown SA et al. 1998).
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Activation of the DNA-bound but transcriptionally incompetent HSF1 is thought to occur upon stress induced HSF1 phosphorylation at several serine residues (Ding XZ et al. 1997; Holmberg CI et al. 2001; Guettouche T et al. 2005). In cells exposed to heat, acquisition of HSE DNA-binding activity was observed to precede phosphorylation of HSF1 (Cotto JJ et al. 1996; Kline MP & Morimoto RI 1997). While there is a sufficient evidence to suggest that phosphorylation of HSF1 is essential to modulate HSF1 transactiviting capacity, mechanisms behind stress stimuli and kinases/phosphatases involved have not been clearly established.
What the reference databases state
Statements
23 statements
23 statements · 1 reference database · Subject: HSF1-dependent transactivation · Sources: Reactome
- AKT1S1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CAMK2A participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CAMK2B participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CAMK2D participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CAMK2G participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CREBBP participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- CRYAB participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- DNAJB1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- EP300 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- FKBP4 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSBP1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSF1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
Show the remaining 11
- HSP90AA1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSP90AB1 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSPA1A participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSPA1L participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSPA2 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSPA8 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- HSPB8 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- MLST8 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- MTOR participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- PTGES3 participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only
- RPTOR participates in HSF1-dependent transactivationProteinReactome R-HSA-3371571Inferred only