HUMAN HEAT-SHOCK FACTOR-1 AND FACTOR-2 ARE DIFFERENTIALLY ACTIVATED AND CAN SYNERGISTICALLY INDUCE HSP70 GENE-TRANSCRIPTION

Two members of the heat shock transcription factor (HSF) family, HSF1 and HSF2, both function as transcriptional activators of heat shock ge ne expression. However, the inducible DNA-binding activities of these two factors are regulated by distinct pathways. HSF1 is activated by h eat shock and other forms of stress, whereas HSF2 is activated during hemin-induced differentiation of human K562 erythroleukemia cells, sug gesting a role for HSF2 in regulating heat shock gene expression under nonstress conditions such as differentiation and development. To unde rstand the distinct regulatory pathways controlling HSF2 and HSF1 acti vities, ive have examined the biochemical and physical properties of t he control and activated states of HSF2 and compared these with the pr operties of HSF1. Our results reveal that the inactive, non-DNA-bindin g forms of HSF2 and HSF1 exist primarily in the cytoplasm of untreated K562 cells as a dimer and monomer, respectively. This difference in t he control oligomeric states suggests that the mechanisms used to cont rol the DNA-binding activities of HSF2 and HSF1 are distinct. Upon act ivation, both factors acquire DNA-binding activity, oligomerize to a t rimeric state, and translocate into the nucleus. Interestingly, we fin d that simultaneous activation of both HSF2 and HSF1 in K562 cells sub jected to hemin treatment followed by heat shock results in the synerg istic induction of hsp70 gene transcription, suggesting a novel level of complex regulation of heat shock gene expression.