The Usf-1 transcription factor is a novel target for the stress-responsivep38 kinase and mediates UV-induced Tyrosinase expression

The stress-activated signalling cascade leading to phosphorylation of the p 38 family of kinases plays a crucial role during development and in the cel lular response to a wide variety of stress-inducing agents. Although altera tions in gene expression characteristic of the stress response require the regulation of key transcription factors by the p38 family, few downstream t argets for this signalling pathway have been identified. By examining the a bility of pigment cells to respond to UV irradiation as part of the UV-indu ced tanning response, we show that while the microphthalmia-associated tran scription factor Mitf regulates basal Tyrosinase expression, it is the ubiq uitous basic helix-loop-helix-leucine zipper transcription factor Usf-1 tha t is required for the UV activation of the Tyrosinase promoter. Consistent with this we demonstrate that Usf-1 is phosphorylated and activated by the stress-responsive p38 kinase. The results suggest that activation of Usf-1 by p38 at a wide variety of viral and cellular promoters will provide a lin k between stimuli as diverse as UV irradiation, glucose, viral infection an d pro-inflammatory cytokines, and the changes in gene expression associated with the stress response.