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First published online 9 June 2009
doi: 10.1242/jcs.036483

Journal of Cell Science 122, 2191-2196 (2009)
Published by The Company of Biologists 2009
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Short Report

A new mechanism of SOX9 action to regulate PKC{alpha} expression in the intestine epithelium

Sébastien Dupasquier1,2,3, Rana Abdel-Samad1,2,3, Robert I. Glazer4, Pauline Bastide1,2,3, Philippe Jay1,2,3, Dominique Joubert1,2,3, Vincent Cavaillès5,6,7,8, Philippe Blache1,2,3 and Corinne Quittau-Prévostel1,2,3,*

1 CNRS,UMR 5203, Institut de Génomique Fonctionnelle, 34094, Montpellier, France
2 INSERM, U661, 34094, Montpellier, France
3 Université Montpellier 1, 2, 34094, Montpellier, France
4 Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA
5 IRCM, Institut de Recherche en Cancérologie de Montpellier, 34298, Montpellier, France
6 INSERM, U896, 34298, Montpellier, France
7 Université Montpellier1, 34298, Montpellier, France
8 CRLC Val d'Aurelle Paul Lamarque, 34298, Montpellier, France

* Author for correspondence (e-mail: Corinne.Quittau-Prevostel{at}igf.cnrs.fr)

Accepted 27 March 2009

Summary

Variations of protein kinase C (PKC) expression greatly influence the proliferation-to-differentiation transition (PDT) of intestinal epithelial cells and might have an important impact on intestinal tumorigenesis. We demonstrate here that the expression of PKC{alpha} in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor. This repression does not require DNA binding of the SOX9 high-mobility group (HMG) domain but is mediated through a new mechanism of SOX9 action requiring the central and highly conserved region of SOXE members. Because SOX9 expression is itself upregulated by Wnt-APC signaling in intestinal epithelial cells, the present study points out this transcription factor as a molecular link between the Wnt-APC pathway and PKC{alpha}. These results provide a potential explanation for the decrease of PKC{alpha} expression in colorectal cancers with constitutive activation of the Wnt-APC pathway.

Key words: Intestine, PKC{alpha}, SOX9, Transcription, Wnt


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© The Company of Biologists Ltd 2009