School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia.
J Biol Chem. 2010 Oct 15;285(42):32405-14. doi: 10.1074/jbc.M110.141317. Epub 2010 Aug 11.
GATA transcription factors have been implicated in controlling adipogenesis in Drosophila and in mammals. In mammals, both GATA2 and GATA3 have been shown to be present in preadipocytes, and their silencing allows the onset of adipogenesis. Overexpression of GATA proteins blocks adipogenesis in cellular assays. GATA factors have been found to operate through recruiting cofactors of the Friend of GATA (FOG) family. FOG proteins, in turn, recruit co-regulators, including C-terminal binding proteins (CTBPs). We have investigated whether FOGs and CTBPs influence adipogenesis. We found that both FOG1 and FOG2 are expressed in cells prior to adipogenesis but are down-regulated as adipogenesis proceeds. Overexpression of FOG1 or FOG2 interferes with adipogenesis. Mutant versions of FOG2 unable to bind CTBP or GATA proteins are impaired in their inability to inhibit adipogenesis. Finally, a mutant version of GATA2, unable to associate with FOGs, also displays abnormal activity and causes enhanced cell proliferation. These results implicate FOGs and CTBPs as partners of GATA proteins in the control of adipocyte proliferation and differentiation.
GATA 转录因子已被牵涉到控制果蝇和哺乳动物的脂肪生成。在哺乳动物中,GATA2 和 GATA3 都被证明存在于前脂肪细胞中,它们的沉默允许脂肪生成的开始。GATA 蛋白的过表达在细胞测定中阻止脂肪生成。已经发现 GATA 因子通过募集 Friend of GATA(FOG)家族的共因子起作用。FOG 蛋白反过来又募集共调节剂,包括 C 端结合蛋白(CTBP)。我们研究了 FOG 和 CTBP 是否影响脂肪生成。我们发现 FOG1 和 FOG2 在脂肪生成之前在细胞中表达,但随着脂肪生成的进行而下调。FOG1 或 FOG2 的过表达干扰脂肪生成。不能结合 CTBP 或 GATA 蛋白的 FOG2 突变体在抑制脂肪生成方面存在缺陷。最后,一种不能与 FOG 结合的 GATA2 突变体也表现出异常活性并导致细胞增殖增强。这些结果表明 FOG 和 CTBP 是 GATA 蛋白在控制脂肪细胞增殖和分化中的伙伴。