Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation.
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 beta-catenin. Whereas beta-catenin coactivates LRH-1 on the cyclin E1 promoter, LRH-1 acts as a potent tissue-restricted coactivator of beta-catenin on the cyclin D1 promoter. The implication of LRH-1 in cell proliferation highlights an unanticipated crosstalk between LRH-1 and the beta-catenin/Tcf4 signaling pathway, which is relevant for the renewal of intestinal crypt cells.
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, 67404 Illkirch, France.
Oronza A
OA
Botrugno
Elisabeth
E
Fayard
Jean-Sébastien
JS
Annicotte
Céline
C
Haby
Thomas
T
Brennan
Olivia
O
Wendling
Toshiya
T
Tanaka
Tatsuhiko
T
Kodama
Winston
W
Thomas
Johan
J
Auwerx
Kristina
K
Schoonjans
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D017690:Cell Transplantation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D019927:Cyclin E; D003598:Cytoskeletal Proteins; C431936:Nr5a2 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1