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J Biol Chem. 2009 Nov 13;284(46):31523-31. doi: 10.1074/jbc.M109.059964. Epub 2009 Sep 21.

Cloning of the human GLI2 Promoter: transcriptional activation by transforming growth factor-beta via SMAD3/beta-catenin cooperation.

Author information

1
INSERM, U697, Université Paris-Diderot, 75010 Paris, France.

Abstract

GLI2 (GLI-Kruppel family member 2), a zinc finger transcription factor that mediates Hedgehog signaling, is implicated in the progression of an ever-growing number of human malignancies, including prostate and pancreatic cancer, as well as basal cell carcinoma of the skin. Its expression is up-regulated by transforming growth factor-beta (TGF-beta) in a variety of cell types, both normal and transformed. We report herein that TGF-beta-driven GLI2 expression is transcriptional and does not result from stabilization of GLI2 transcripts. We describe the characterization of the 5'-flanking sequence of human GLI2 mRNA, the identification of a transcription start site, the cloning of approximately 1,600 bp of the regulatory promoter region and the identification and functional analysis of a TGF-beta-responsive region mapped to a 91-bp sequence between nucleotides -119 and -29 of the promoter. This region harbors SMAD and lymphoid enhancer factor/T cell factor binding sites that allow functional cooperation between SMAD3 and beta-catenin, recruited to the promoter in response to TGF-beta to drive GLI2 gene transcription.

PMID:
19797115
PMCID:
PMC2797221
DOI:
10.1074/jbc.M109.059964
[Indexed for MEDLINE]
Free PMC Article

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