The proto-oncogeneJUNis a target of the heat shock transcription factor HSF1


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Abstract

The transcription factor activator protein-1 (AP-1) participates in many aspects of cell physiology, such as cellular proliferation, transformation, and death. AP-1 is a dimeric complex that primarily contains Jun and Fos family members. Here, we report that JUN is a target of heat shock transcription factor HSF1. HSF1 is the master regulator of genes encoding molecular chaperones, and is involved in cellular processes such as the stress response, cell differentiation, aging and carcinogenesis. In HeLa cells, JUN transcription was rapidly induced by heat treatment. We found that HSF1 bound to the JUN promoter and was necessary for its efficient response to heat shock. In heat-shocked cells, c-Jun-mediated gene expression was induced slowly following accumulation of c-Jun protein. Forced expression of active HSF1 in cells resulted in an increase in c-Jun expression and activation of c-Jun target genes. These results show that HSF1 regulates JUN expression, thereby modulating AP-1 activity.JUNis a heat-inducible gene that contains an HSF1-binding sequence in the promoter region. HSF1 binds to the JUN promoter and is necessary for its efficient response to heat shock. Moreover, forced expression of constitutively active HSF1 in cells leads to an increase in c-Jun expression and the activation of c-Jun target genes, CCND1 and CD44.

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