Prokaryotic and eukaryotic cells respond to thermal and chemical stress by inducing a group of genes collectively designated heat shock genes. In eukaryotes, this gene expression is regulated primarily at the transcription level. Heat shock transcription factors (HSF, also designated HSTF) 1 and 2 are involved in this regulation. HSF1 and HSF2 are upregulated by estrogen at both the mRNA and protein level. HSF1 is normally found as a monomer whose transcriptional activity is repressed by constitutive phosphorylation. Upon activation, HSF1 forms trimers, gains DNA binding activity and is translocated to the nucleus. HSF2 activity is associated with differentiation and development, and, like HSF1, binds DNA as a trimer. Both HSF1 and HSF2 are known to be induced by proteasome inhibitors of the ubiquitin pathway.