SUMMARY PARAGRAPH for HSF1
HSF1 encodes a transcription factor that regulates transcription in response to stress (7). Best known for its involvement in heat shock response, Hsf1p regulates the transcription of hundreds of targets, including genes involved in protein folding, detoxification, energy generation, carbohydrate metabolism, and cell wall organization (8, 9). Deletion of HSF1 is lethal and mutants are defective in several processes including maintenance of cell wall integrity, spindle pole body duplication, protein transport, and cell cycle progression (1, 10, 11, 12).
Hsf1p binds in both constitutive and inducible manners to the conserved heat shock element (HSE) motif found in the promoters of its target genes as a homotrimeric complex; each individual monomer recognizes the 5-bp sequence, 5'-NGAAN-3' (1, 13, 14). HSEs fall into one of three categories depending on the organization of the NGAAN motifs: ''Perfect'' HSEs consist of three or more contiguous repeats of the motif, ''gap'' HSEs consists of a 5-bp gap separating two contiguous motifs from a third one, and ''step'' HSEs contain 5-bp gaps separating each of the three motifs (5 and references contained therein).
In unstressed cells Hsf1p is constitutively phosphorylated, but under certain stresses, such as alkaline pH, increased concentrations of salicylate, oxidative stress, heat stress, or glucose starvation, it becomes hyperphosphorylated and adopts an activated conformation resulting in the transcription of target genes (15, and reviewed in 16). Glucose starvation-induced hyperphosphorylation is mediated by the AMP-activated kinase Snf1p (17).
Hsf1p includes a winged-helix-turn-helix DNA-binding domain (DBD) (18), a hydrophobic repeat region necessary for coiled-coil formation during Hsf1p oligomerization (19), N-terminal and C-terminal trans-activation domains (AR1 and AR2) (20, 21), the negative regulatory domain conserved element 2 (CE2) (22), and the C-terminal modulator (CTM) domain which alleviates CE2 repression (23). In addition to binding HSE motifs, the DBD negatively regulates Hsf1p transcriptional activity (2). AR1 is thought to mediate the response to transient heat shock while AR2 is thought to mediate response to sustained heat stress (21). AR2 and CTM are also necessary for mediating transcription of genes with gap-type HSEs (23, 24).
The general structure and function of heat shock factors are conserved between eukaryotic organisms, but the number and importance of HSF genes varies. HSF1 homologs have been identified in S. pombe, D. melanogaster, chickens, plants, and mammals (9 and references therein). Mammalian HSF1 is involved in the processes of stress-induced transcription, extra-embryonic development, and postnatal growth (25).
Last updated: 2006-11-13