MOLECULAR CHAPERONES AS HSF1-SPECIFIC TRANSCRIPTIONAL REPRESSORS

The rapid yet transient transcriptional activation of heat shock genes is mediated by the reversible conversion of HSF1 from an inert negati vely regulated monomer to a transcriptionally active DNA-binding trime r. During attenuation of the heat shock response, transcription of hea t shock genes returns to basal levels and HSF1 reverts to an inert mon omer. These events coincide with elevated levels of Hsp70 and other he at shock proteins (molecular chaperones). Here, we show that the molec ular chaperone Hsp70 and the cochaperone Hdj1 interact directly with t he transactivation domain of HSF1 and repress heat shock gene transcri ption. Overexpression of either chaperone represses the transcriptiona l activity of a transfected GAL4-HSF1 activation domain fusion protein and endogenous HSF1. As neither the activation of HSF1 DNA binding no r inducible phosphorylation of HSF1 was affected, the primary autoregu latory role of Hsp70 is to negatively regulate HSF1 transcriptional ac tivity. These results reveal that the repression of heat shock gene tr anscription, which occurs during attenuation, is due to the associatio n of Hsp70 with the HSF1 transactivation domain, thus providing a plau sible explanation for the role of molecular chaperones in at least one key step in the autoregulation of the heat shock response.