Heat shock transcription factor, HSF

In virtually all organisms, enhanced synthesis of heat shock proteins (HSPs) occurs in response to environmental, chemical, and physiological stresses. Some members of the evolutionarily conserved HSP gene family are constitutively expressed and function as molecular chaperones. It has been demonstrated that HSP induction results primarily from the activation of a heat shock transcription factor (HSF) with subsequent binding to heat shock response DNA elements (HSEs) in the enhancer regions of the HSP genes157. Heat shock responses in fish have been recently reviewed by Basu et al.15 and will be discussed in another chapter of this volume, so we will primarily limit our discussions to heat shock responses in zebrafish. 

Heat shock transcription factor (HSF) is part of the family of heat shock factors that are activated and bind to DNA induced by OS. Several chemicals, heat shock, or conditions that generate abnormally folded proteins activate HSFl conversion from a monomer to a trimer state (Liu et al., 1996). lodoacetamide (IDAM), an alkylating agent, activates the transcription of Hsp 70 gene (Liu et al., 1996). The depletion of GSH induces oxidation of protein thiols, denaturation, and aggregation of proteins (Freeman et al., 1997). Alkylating agents that deplete GSH increase HSFl (Liu et al., 1996) and induce trimerization of HSFl. 

Induction of heat-shock proteins depends upon a heat-shock promoter element (HSE) that binds an activating transcription factor HSF.452-455 An increase in temperature not only induces synthesis of heat-shock proteins but represses synthesis of most other proteins. Thus, in E. coli or Salmonella a shift from 30°C to 42°C causes the appearance of 13 heat-shock proteins. At 50°C synthesis of almost all other proteins stops. In E. coli transcription of heat-shock genes is controlled by alternative factors, o32 and oE.456 456a... 

FIGURE 5 Activation of transcription of heat-shock genes in mammalian cells. The heat shock factor (HSF) is present as a monomer in normal cells. An increase in temperature results in a trimerization of HSF, which binds to the heat shock element (HSE). HSF is activated as a transcriptional enhancer protein by phosphorylation. 

TF transcription factor, R receptor, Fur ferric uptake regulation protein, NF-kB nuclear factor-kB, AP-1 activator protein-1, Egr-1 early growth response-1, VDR la,25-dihydroxy-vitamin D3 receptor, RXR retinoid X receptor, PPARy peroxisome proliferator-activated receptor y NFAT nuclear factor of activated T-cells, HSF heat shock factor, p53 tumor suppressor p53, HIF-1 hypoxia inducible factor-1. ... 

The enhanced expression of metal-induced stress proteins is controlled primarily at the transcriptional level similar to the induction of hsps by heat (Wu et al. 1986). Regulation of hsp genes in eukaryotic systems is mediated by a cw-acting heat shock control element (HSE) that is found in multiple copies upstream of the transcriptional start site (Pelham 1982). Transcriptional activation of the hsp genes is mediated by a ran -acting protein, known as the heat shock factor (HSF), which binds specifically to the HSE (Wu 1984a,b). 

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