HEAT-SHOCK FACTOR-1 REPRESSES RAS-INDUCED TRANSCRIPTIONAL ACTIVATION OF THE C-FOS GENE

Heat shock factor 1, the critical molecular regulator of the stress re sponse is conserved throughout eukaryotic organisms and activates the transcription of heat shock genes. We now show that heat shock factor 1 inhibits the expression of c-fos, an immediate early gene that contr ols responses to extracellular stimuli for growth and differentiation. Heat shock factor 1 inhibits the transcription of the c-fos gene and antagonizes the activating effects of the signal transducing protein H as on the c-fos promoter and on the promoter of another Has responsive gene uPA. This property was specific for heat shock factor 1; c-fos r epression was not seen with the structurally related protein heat shoc k factor 2, Repression involved different molecular mechanisms compare d with those involved in transcriptional activation by heat shock fact or 1 and specifically did not require binding to the c-fos promoter. T hus, in addition to its known role as a transcriptional activator of t he cellular heat shock response, heat shock factor 1 also antagonizes the expression of Fos, a key component of the ubiquitous AP-1 transcri ption factor complex and as such could influence multiple aspects of c ell regulation.