HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene.
Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation.
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Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston MA 02115, USA.
Chen
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Xie
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Asea
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Calderwood
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D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D016762:Genes, fos / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics; D018832:Molecular Chaperones / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D018832:Molecular Chaperones; D014157:Transcription Factors; D008156:Luciferases