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PMID: 19389701 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Target gene specificity of USF-1 is directed via p38-mediated phosphorylation-dependent acetylation.

The Journal of biological chemistry ·Vol. 284 ·No. 28 ·2009-07-10 ·Pages 18851-62

Corre S, Primot A, Baron Y, Le Seyec J, Goding C, Galibert MD

Abstract

How transcription factors interpret the output from signal transduction pathways to drive distinct programs of gene expression is a key issue that underpins development and disease. The ubiquitously expressed basic-helix-loop-helix leucine zipper upstream stimulating factor-1 binds E-box regulatory elements (CANNTG) to regulate a wide number of gene networks. In particular, USF-1 is a key component of the tanning process. Following UV irradiation, USF-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the POMC, MC1R, TYR, TYRP-1 and DCT genes. However, how phosphorylation on Thr-153 might affect the activity of USF-1 is unclear. Here we show that, in response to DNA damage, oxidative stress and cellular infection USF-1 is acetylated in a phospho-Thr-153-dependent fashion. Phospho-acetylated USF-1 is nuclear and interacts with DNA but displays altered gene regulatory properties. Phospho-acetylated USF-1 is thus proposed to be associated with loss of transcriptional activation properties toward several target genes implicated in pigmentation process and cell cycle regulation. The identification of this critical stress-dependent USF-1 modification gives new insights into understanding USF-1 gene expression modulation associated with cancer development.

MeSH Terms
Acetylation Amino Acid Sequence Animals DNA Damage Gene Expression Regulation Humans Melanoma, Experimental Mice Molecular Sequence Data Oxidative Stress Phosphorylation Protein Processing, Post-Translational Threonine/chemistry Upstream Stimulatory Factors/metabolism,physiology p38 Mitogen-Activated Protein Kinases/metabolism
Chemicals
USF1 protein, human Upstream Stimulatory Factors Threonine p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Corre Sébastien
Signaling and Development Laboratory, Marie Curie Research Institute, The Chart, Oxted RH8 OTL, United Kingdom.
Primot Aline
Baron Yorann
Le Seyec Jacques
Goding Colin
Galibert Marie-Dominique
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M808605200
Published
2009-07-10
Epub
2009-00-23
Pages
18851-62
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2707245
Subset
IM
External Links
PubMed source DOI: 10.1074/jbc.M808605200 PMC Full Text View journal details
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