Synergy between LRH-1 and β-catenin Induces G1 cyclin-mediated cell proliferation

Oronza A. Botrugno, Elisabeth Fayard, Jean Sébastien Annicotte, Céline Haby, Thomas Brennan, Olivia Wendling, Toshiya Tanaka, Tatsuhiko Kodama, Winston Thomas, Johan Auwerx, Kristina Schoonjans

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Abstract

LRH-1 is an orphan nuclear receptor predominantly expressed in tissues of endodermal origin, where it controls development and cholesterol homeostasis. We show here that LRH-1 induces cell proliferation through the concomitant induction of cyclin D1 and E1, an effect that is potentiated by its interaction with β-catenin. Whereas β-catenin coactivates LRH-1 on the cyclin E1 promoter, LRH-1 acts as a potent tissue-restricted coactivator of β-catenin on the cyclin D1 promoter. The implication of LRH-1 in cell proliferation highlights an unanticipated crosstalk between LRH-1 and the β-catenin/Tcf4 signaling pathway, which is relevant for the renewal of intestinal crypt cells.

Original languageEnglish
Pages (from-to)499-509
Number of pages11
JournalMolecular Cell
Volume15
Issue number4
DOIs
Publication statusPublished - Aug 27 2004

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ASJC Scopus subject areas

  • Molecular Biology

Cite this

Botrugno, O. A., Fayard, E., Annicotte, J. S., Haby, C., Brennan, T., Wendling, O., Tanaka, T., Kodama, T., Thomas, W., Auwerx, J., & Schoonjans, K. (2004). Synergy between LRH-1 and β-catenin Induces G1 cyclin-mediated cell proliferation. Molecular Cell, 15(4), 499-509. https://doi.org/10.1016/j.molcel.2004.07.009