The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression.
The stress-activated signalling cascade leading to phosphorylation of the p38 family of kinases plays a crucial role during development and in the cellular response to a wide variety of stress-inducing agents. Although alterations in gene expression characteristic of the stress response require the regulation of key transcription factors by the p38 family, few downstream targets for this signalling pathway have been identified. By examining the ability of pigment cells to respond to UV irradiation as part of the UV-induced tanning response, we show that while the microphthalmia-associated transcription factor Mitf regulates basal Tyrosinase expression, it is the ubiquitous basic helix-loop-helix-leucine zipper transcription factor Usf-1 that 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 link between stimuli as diverse as UV irradiation, glucose, viral infection and pro-inflammatory cytokines, and the changes in gene expression associated with the stress response.
Galibert
M D
MD
Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted RH8 0TL, UK.
Carreira
S
S
Goding
C R
CR
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000502:physiology; D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects*; D017930:Genes, Reporter; D005982:Glutathione Transferase / Q000235:genetics; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008545:Melanoma; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000528:radiation effects; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D051720:Upstream Stimulatory Factors; D048051:p38 Mitogen-Activated Protein Kinases
D002843:Chromatin; D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; D051720:Upstream Stimulatory Factors; C497183:Usf1 protein, mouse; D014442:Monophenol Monooxygenase; D005982:Glutathione Transferase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases