Human heat shock factors 1 and 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 gene expression. However, the inducible DNA-binding activities of these two factors are regulated by distinct pathways. HSF1 is activated by heat shock and other forms of stress, whereas HSF2 is activated during hemin-induced differentiation of human K562 erythroleukemia cells, suggesting a role for HSF2 in regulating heat shock gene expression under nonstress conditions such as differentiation and development. To understand the distinct regulatory pathways controlling HSF2 and HSF1 activities, we have examined the biochemical and physical properties of the control and activated states of HSF2 and compared these with the properties of HSF1. Our results reveal that the inactive, non-DNA-binding forms of HSF2 and HSF1 exist primarily in the cytoplasm of untreated K562 cells as a dimer and monomer, respectively. This difference in the control oligomeric states suggests that the mechanisms used to control the DNA-binding activities of HSF2 and HSF1 are distinct. Upon activation, both factors acquire DNA-binding activity, oligomerize to a trimeric state, and translocate into the nucleus. Interestingly, we find that simultaneous activation of both HSF2 and HSF1 in K562 cells subjected to hemin treatment followed by heat shock results in the synergistic induction of hsp70 gene transcription, suggesting a novel level of complex regulation of heat shock gene expression.
Sistonen
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L
Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208.
Sarge
K D
KD
Morimoto
R I
RI
D002451:Cell Compartmentation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D014157:Transcription Factors; C070389:HSF2 protein, human; D006427:Hemin