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 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Division / physiology*
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Cell Line
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Cell Transplantation
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Cyclin D1 / genetics
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Cyclin D1 / metabolism*
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Cyclin E / genetics
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Cyclin E / metabolism*
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Cytoskeletal Proteins / metabolism*
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G1 Phase*
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Gene Expression Regulation
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Humans
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Intestinal Mucosa / cytology
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Intestinal Mucosa / physiology
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Mice
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Mice, Nude
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Mice, Transgenic
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Receptors, Cytoplasmic and Nuclear / genetics
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Retroviridae / genetics
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Retroviridae / metabolism
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Signal Transduction / physiology
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Trans-Activators / metabolism*
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beta Catenin
Substances
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Cyclin E
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Cytoskeletal Proteins
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Nr5a2 protein, mouse
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Receptors, Cytoplasmic and Nuclear
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Trans-Activators
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beta Catenin
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Cyclin D1