16 Structure and Regulation of Heat Shock Transcription Factor

Abstract

I. INTRODUCTION
The transcriptional induction of heat shock genes by elevated temperatures and other forms of physiological stress in eukaryotes is mediated by the transcription factor heat shock factor (HSF). Considerable progress in our understanding of the structure of HSF and how its activity is regulated by heat shock has been achieved since the identification and purification of HSF proteins from a variety of metazoan species. For a review of the early studies, see Lis et al. (1990) and Wu et al. (1990). Here, we summarize recent advances in the structure and regulation of HSF, drawing primarily from studies in our laboratory on the Drosophila and human HSF proteins. Further elaborations on HSF, including the multiplicity of HSF genes and how heat shock promoters are poised to respond to HSF binding, are treated elsewhere in this volume (see Sarge et al.; Lis et al.).

II. DNA BINDING BY A MONOMER-TRIMER TRANSITION
Like many inducible transcriptional regulators, the HSF protein is synthesized constitutively and stored in a latent form under normal conditions. This property of HSF, originally observed for human and Drosophila HSF proteins (Kingston et al. 1987; Zimarino and Wu 1987), appears to be common to all eukaryotic species studied. With the exception of budding yeasts, the latent HSF is activated in response to heat shock by the acquisition of high-affinity DNA-binding activity, which is accomplished by a conversion of HSF protein from a monomer to a homotrimer (Perisic et al. 1989; Westwood et al. 1991; Baler et al. 1993;...