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PMID: 11532965 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Usf-1 transcription factor is a novel target for the stress-responsive p38 kinase and mediates UV-induced Tyrosinase expression.

The EMBO journal ·Vol. 20 ·No. 17 ·2001-09-03 ·Pages 5022-31

Galibert MD, Carreira S, Goding CR

Abstract

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.

MeSH Terms
3T3 Cells Animals COS Cells Chlorocebus aethiops Chromatin/physiology DNA-Binding Proteins Gene Expression Regulation, Enzymologic/radiation effects Genes, Reporter Glutathione Transferase/genetics Helix-Loop-Helix Motifs Humans Melanocytes/cytology,metabolism,radiation effects Melanoma Mice Mitogen-Activated Protein Kinases/metabolism Monophenol Monooxygenase/genetics Promoter Regions, Genetic/radiation effects Recombinant Fusion Proteins/analysis Transcription Factors/metabolism Transfection Tumor Cells, Cultured Ultraviolet Rays Upstream Stimulatory Factors p38 Mitogen-Activated Protein Kinases
Chemicals
Chromatin DNA-Binding Proteins Recombinant Fusion Proteins Transcription Factors USF1 protein, human Upstream Stimulatory Factors Usf1 protein, mouse Monophenol Monooxygenase Glutathione Transferase Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Galibert M D
Eukaryotic Transcription Laboratory, Marie Curie Research Institute, The Chart, Oxted RH8 0TL, UK.
Carreira S
Goding C R
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.17.5022
Published
2001-09-03
Pages
5022-31
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125271
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.17.5022 PMC Full Text View journal details
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