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J Biol Chem
2009 Oct 30;28444:30097-104. doi: 10.1074/jbc.M109.049304.
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Human BAMBI cooperates with Smad7 to inhibit transforming growth factor-beta signaling.
Yan X, Lin Z, Chen F, Zhao X, Chen H, Ning Y, Chen YG.
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Transforming growth factor beta (TGF-beta) and related growth factors are essential regulators of embryogenesis and tissue homeostasis. The signaling pathways mediated by their receptors and Smad proteins are precisely modulated by various means. Xenopus BAMBI (bone morphogenic protein (BMP) and activin membrane-bound inhibitor) has been shown to function as a general negative regulator of TGF-beta/BMP/activin signaling. Here, we provide evidence that human BAMBI (hBAMBI), like its Xenopus homolog, inhibits TGF-beta- and BMP-mediated transcriptional responses as well as TGF-beta-induced R-Smad phosphorylation and cell growth arrest, whereas knockdown of endogenous BAMBI enhances the TGF-beta-induced reporter expression. Mechanistically, in addition to interfering with the complex formation between the type I and type II receptors, hBAMBI cooperates with Smad7 to inhibit TGF-beta signaling. hBAMBI forms a ternary complex with Smad7 and the TGF-beta type I receptor ALK5/TbetaRI and inhibits the interaction between ALK5/TbetaRI and Smad3, thus impairing Smad3 activation. These findings provide a novel insight to understand the molecular mechanism underlying the inhibitory effect of BAMBI on TGF-beta signaling.
Boyd,
Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor.
1989, Pubmed
Boyd,
Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor.
1989,
Pubmed Cárcamo,
Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin.
1994,
Pubmed Chen,
The TGF-beta pseudoreceptor gene Bambi is dispensable for mouse embryonic development and postnatal survival.
2007,
Pubmed
,
Xenbase Degen,
Expression of nma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts.
1996,
Pubmed Deheuninck,
Ski and SnoN, potent negative regulators of TGF-beta signaling.
2009,
Pubmed Dennler,
Direct binding of Smad3 and Smad4 to critical TGF beta-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene.
1998,
Pubmed Derynck,
TGF-beta signaling in tumor suppression and cancer progression.
2001,
Pubmed Derynck,
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
2003,
Pubmed Ebisawa,
Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation.
2001,
Pubmed Feng,
Specificity and versatility in tgf-beta signaling through Smads.
2005,
Pubmed Goumans,
TGF-beta signaling in vascular biology and dysfunction.
2009,
Pubmed Grotewold,
Bambi is coexpressed with Bmp-4 during mouse embryogenesis.
2001,
Pubmed
,
Xenbase Guo,
Signaling cross-talk between TGF-beta/BMP and other pathways.
2009,
Pubmed Hayashi,
The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling.
1997,
Pubmed Higashihori,
Expression and regulation of the decoy bone morphogenetic protein receptor BAMBI in the developing avian face.
2008,
Pubmed Hill,
Nucleocytoplasmic shuttling of Smad proteins.
2009,
Pubmed Huang,
Identification of a potential regulator of early transcriptional responses to mesoderm inducers in the frog embryo.
1995,
Pubmed
,
Xenbase Imamura,
Smad6 inhibits signalling by the TGF-beta superfamily.
1997,
Pubmed Itoh,
Negative regulation of TGF-beta receptor/Smad signal transduction.
2007,
Pubmed Karaulanov,
Transcriptional regulation of BMP4 synexpression in transgenic Xenopus.
2004,
Pubmed
,
Xenbase Kavsak,
Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation.
2000,
Pubmed
,
Xenbase Khin,
BAMBI gene is epigenetically silenced in subset of high-grade bladder cancer.
2009,
Pubmed Lin,
The pseudoreceptor BMP and activin membrane-bound inhibitor positively modulates Wnt/beta-catenin signaling.
2008,
Pubmed Lönn,
Regulating the stability of TGFbeta receptors and Smads.
2009,
Pubmed Loveland,
Expression of Bambi is widespread in juvenile and adult rat tissues and is regulated in male germ cells.
2003,
Pubmed Massagué,
Smad transcription factors.
2005,
Pubmed Massagué,
TGF-beta signal transduction.
1998,
Pubmed Massagué,
Controlling TGF-beta signaling.
2000,
Pubmed Massagué,
TGFbeta signaling in growth control, cancer, and heritable disorders.
2000,
Pubmed Miyazono,
Regulation of TGF-beta signaling and its roles in progression of tumors.
2003,
Pubmed Miyazono,
Positive and negative regulation of TGF-beta signaling.
2000,
Pubmed Moustakas,
Smad regulation in TGF-beta signal transduction.
2001,
Pubmed Nakao,
Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling.
1997,
Pubmed
,
Xenbase Onichtchouk,
Silencing of TGF-beta signalling by the pseudoreceptor BAMBI.
1999,
Pubmed
,
Xenbase Padua,
Roles of TGFbeta in metastasis.
2009,
Pubmed Park,
Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads.
2005,
Pubmed Sasaki,
Effect of Nma on growth inhibition by TGF-betaa in human gastric carcinoma cell lines.
2004,
Pubmed Schmierer,
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
2007,
Pubmed Seki,
TLR4 enhances TGF-beta signaling and hepatic fibrosis.
2007,
Pubmed Sekiya,
Identification of BMP and activin membrane-bound inhibitor (BAMBI), an inhibitor of transforming growth factor-beta signaling, as a target of the beta-catenin pathway in colorectal tumor cells.
2004,
Pubmed Sekiya,
Transcriptional regulation of the TGF-beta pseudoreceptor BAMBI by TGF-beta signaling.
2004,
Pubmed
,
Xenbase Shi,
GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor.
2004,
Pubmed Souchelnytskyi,
Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors.
1998,
Pubmed
,
Xenbase Suzuki,
Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane.
2002,
Pubmed ten Dijke,
New insights into TGF-beta-Smad signalling.
2004,
Pubmed Tsang,
Zebrafish nma is involved in TGFbeta family signaling.
2000,
Pubmed
,
Xenbase Watabe,
Roles of TGF-beta family signaling in stem cell renewal and differentiation.
2009,
Pubmed Wrighton,
Phospho-control of TGF-beta superfamily signaling.
2009,
Pubmed Xi,
Genome-wide impact of the BRG1 SWI/SNF chromatin remodeler on the transforming growth factor beta transcriptional program.
2008,
Pubmed Yan,
Regulation of TGF-beta signaling by Smad7.
2009,
Pubmed Zhang,
Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation.
2007,
Pubmed
