转化生长因子β(TGF-β)及其相关的生长因子为胚胎发育和组织稳态所必需。Smads和受体以各种方式对其信号进行调节。已经证实在爪蟾胚胎发育过程中，BAMBI能够调控TGF-β、BMP和activin信号。我们的研究表明，人类BAMBI基因和爪蟾一样，也能作为TGF-β家族的通用抑制因子，说明BAMBI的功能在进化过程中高度保守。进一步的实验表明，BAMBI能够和TGF-β Ⅰ型受体以及Smad7发生相互作用。免疫共沉淀分析表明，BAMBI不但能够干扰TGF-β Ⅰ型和Ⅱ型受体复合物的形成,还可以加强Smad7和TGF-β Ⅰ型受体之间的相互作用。最后，我们证实，过量表达BAMBI能够减弱TGF-β诱导的细胞生长阻滞以及促进细胞迁移的作用。 Wnt/Wingless信号途径通过调控细胞命运、增殖和分化，在胚胎发育和维持成年动物组织稳态方面发挥着重要作用，并且在多种癌症中受到异常的活化。最近有人发现BAMBI能够作为β-catenin的靶基因，在结直肠癌和肝癌中β -catenin能够诱导其表达。然而没有人报道BAMBI是否以及怎样调控Wnt信号。在本研究中，我们首先用报告基因分析的方法证明BAMBI能促进Wnt信号。接着用RNA干扰的方法抑制BAMBI基因的表达，能够减弱响应于Wnt信号的报告基因的活性。此外，我们证明它能够加强受体和Dishevelled的相互作用，从而导致信号的增加。最后，我们证明BAMBI能够诱导Wnt信号靶基因c-myc和cyclm D1的表达并且能够促进细胞生长。 BAMBI是TGF-β信号的伪受体，它本身的表达受TGF-β和Wnt信号通路的双重调节。反之，BAMBI也可以调控这两条信号通路，从而可能在细胞生长和疾病发生过程中发挥重要作用。 关键词：BAMBI；TGF-β；Smad7；Wnt；Dvl-2

 Transforming growth factor β(TGF-β) and related growth factors are essential regulators of embryogenesis and tissue homeostasis. The signaling pathway mediated by their receptors and Smad proteins is precisely modulated by various means. BAMBI has been shown to negatively regulate the signaling activity of TGF-β, BMP, and activin in Xenopus embryos. Here, we provide evidence that human BAMBI, like its Xenopus homolog, inhibits the transcriptional response of TGF-β signaling, suggesting an evolutionally conserved activity of BAMBI. We further show that human BAMBI can interact with TGF-β receptors as well as the inhibitory Smad7. Immunoprecipitation assay revealed that BAMBI not only impairs the heterocomplex formation of TGF-β type Ⅰ and type Ⅱ receptors, but also enhance the binding of Smad7 to TGF-β type Ⅰ receptor. Finally, we demonstrate that human BAMBI can attenuate TGF-β-induced cell growth and cell migration. The Wnt/Wingless pathway plays a pivotal role in embryonic development and adult homeostasis by regulating cell fate, proliferation, and differentiation, and it is aberrantly reactivated in various human cancers. Recently BAMBI had been identified as a target of β-catenin, which could directly induce its expression in colorectal and hepatocellular tumor cells. However, whether and how this protein regulates Wnt signaling remains a complete mystery. In this study, we firstly demonstrated that BAMBI can promote Wnt signaling by reporter assays. Blocking the expression of BAMBI protein by small interfering RNA can decrease the signaling activity of Wnt-responsive reporters. Furthermore, we also show that it can enhance the association of Wnt signaling receptor and Dv1-2, leading to the increase of Wnt signaling. Finally we show that BAMBI can induce Wnt target gene expression such as c-myc and cyclin D1 and promote the cell growth. BAMBI, a pseudoreceptor of TGF-β signaling, can be induced by both TGF-β and Wnt signaling pathway and it also exerts an effect on their downstream signaling events, thus playing an important role in the regulation of cell growth and pathogenesis. Keyword: BAMBI; TGF-β; Smad7; Wnt; Dv1-2