Heat shock control factor

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). 

It transpires that the heat shock genes of one single bacterial species are regulated by different mechanisms. Genes and operons controlled by one particular regulator are called regulons and, if there are at least two regulons in one species induced by the same stress factor, they form a stimulon. 

The rpoH gene is expressed from four different promoters. Under normal physiological conditions, the PI promoter is responsible for most of the rpoH transcription, while P2 and P4 promoters contribute varying minor amounts. The P3 promoter is under the control of the Eo holoenzyme (see below) and becomes induced at temperatures above 45 °C. The rpoH gene is expressed at all temperatures, and after a heat shock its transcription is increased by a factor of 1.5 only, but there is a large transient increase in intracellular levels. Two factors contribute significantly to this increase an enhanced rate of translation of the rpoH mRNA, and a transient stabilization in the half-life of... 

Fig. 4.4. The principle of signal transduction by nuclear receptors. Nuclear receptors are ligand-controlled transcription factors that bind cognate DNA sequences, or hormone responsive elements (HRE). The hormone acts as a regulating ligand. Most nuclear receptors bind their cognate HREs, which tend to be symmetrically organized, as homo- or heterodimers. The DNA-bound, activated receptor stimulates transcription initiation via direct or indirect protein-protein interactions with the transcription initiation complex. The arrows demonstrate the different possible configurations of the HRE (see also 4.6). H hormone Hsp heat shock protein.

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... 

Cellular control of HSP expression All HSPs are regulated by a small family of transcription factors called heat shock factor (HSFl ). During a stress condition, HSFl and 2 are hyperphosphorylated in a ras-dependent manner by MAP kinases. Binding of these active HSFl factors to DNA sequences called heat shock elements in the promoters of all stress-inducible genes occurs. This leads to increased transcription of HSP genes and induction of HSP proteins. 

TRANSLATIONAL CONTROL Eukaryotic cells can respond to various stimuli (e.g., heat shock, viral infections, and cell cycle phase changes) by selectively altering protein synthesis. The covalent modification of several translation factors (nonribosomal proteins that assist in the translation process) has been observed to alter the overall protein synthesis rate and/or enhance the translation of specific mRNAs. For example, the phosphorylation of the protein eIF-2 affects the rate of hemoglobin synthesis in rabbit reticulocytes (immature red blood cells). 

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