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 response 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 controls 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 Ras on the c-fos promoter and on the promoter of another Ras responsive gene uPA. This property was specific for heat shock factor 1; c-fos repression was not seen with the structurally related protein heat shock factor 2. Repression involved different molecular mechanisms compared with those involved in transcriptional activation by heat shock factor 1 and specifically did not require binding to the c-fos promoter. Thus, in addition to its known role as a transcriptional activator of the cellular heat shock response, heat shock factor 1 also antagonizes the expression of Fos, a key component of the ubiquitous AP-1 transcription factor complex and as such could influence multiple aspects of cell regulation.
Chen
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Dana-Farber Cancer Institute and Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 02115, USA.
Xie
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Y
Stevenson
M A
MA
Auron
P E
PE
Calderwood
S K
SK
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D017930:Genes, Reporter; D016762:Genes, fos; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D016760:Proto-Oncogene Proteins c-fos; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C070389:HSF2 protein, human; D008156:Luciferases; D001616:beta-Galactosidase; D014568:Urokinase-Type Plasminogen Activator; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)