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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.

Original publication

DOI

10.1093/emboj/20.17.5022

Type

Journal article

Journal

EMBO J

Publication Date

03/09/2001

Volume

20

Pages

5022 - 5031

Keywords

3T3 Cells, Animals, COS Cells, Cercopithecus aethiops, Chromatin, DNA-Binding Proteins, Gene Expression Regulation, Enzymologic, Genes, Reporter, Glutathione Transferase, Helix-Loop-Helix Motifs, Humans, Melanocytes, Melanoma, Mice, Mitogen-Activated Protein Kinases, Monophenol Monooxygenase, Promoter Regions, Genetic, Recombinant Fusion Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Ultraviolet Rays, Upstream Stimulatory Factors, p38 Mitogen-Activated Protein Kinases