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Mol. Cell. Biol. doi:10.1128/MCB.01640-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Chibby Promotes Adipocyte Differentiation through Inhibition of -Catenin Signaling

Department of Pharmacology, Graduate Program in Genetics, and Graduate Program in Molecular and Cellular Pharmacology, SUNY at Stony Brook, New York 11794; Department of Pathology, University of Florida, Gainesville, Florida 32610; and Department of Pharmacology, HHMI, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98195

^* To whom correspondence should be addressed. Email: takemaru{at}pharm.sunysb.edu.

	Abstract

The canonical Wnt/-catenin signaling pathway plays diverse roles in embryonic development and disease. Activation of this pathway, likely by Wnt-10b, has been shown to inhibit adipogenesis in cultured 3T3-L1 preadipocytes and in mice. Here we report that the -catenin antagonist Chibby (Cby) is required for adipocyte differentiation. Cby is expressed in adipose tissue in mice, and Cby protein levels increase during adipogenic differentiation of 3T3-L1 cells. Ectopic expression of Cby induces spontaneous differentiation of these cells into mature adipocytes to a similar extent as dominant-negative Tcf-4. In contrast, depletion of Cby by RNA interference potently blocks adipogenesis of 3T3-L1 and mouse embryonic stem cells. Supportingly, embryonic fibroblasts obtained from Cby-deficient embryos display attenuated differentiation to the adipogenic lineage. Mechanistically, Cby promotes adipocyte differentiation in part by inhibiting -catenin since gain- or loss-of-function of Cby influences -catenin signaling in 3T3-L1 cells. Our results therefore establish Cby as a novel proadipogenic factor required for adipocyte differentiation.

This article has been cited by other articles:

• Li, F.-Q., Mofunanya, A., Harris, K., Takemaru, K.-I. (2008). Chibby cooperates with 14-3-3 to regulate {beta}-catenin subcellular distribution and signaling activity. J. Cell Biol. 181: 1141-1154 [Abstract] [Full Text]