Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The TGFβ signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGFβ ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGFβ1 signaling. Coco synergizes with TGFβ1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGFβ1 and enhances TGFβ1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGFβ signaling.
Arduini,
Modulation of FOXD3 activity in human embryonic stem cells directs pluripotency and paraxial mesoderm fates.
2012, Pubmed
Arduini,
Modulation of FOXD3 activity in human embryonic stem cells directs pluripotency and paraxial mesoderm fates.
2012,
Pubmed
Bates,
Coco regulates dorsoventral specification of germ layers via inhibition of TGFβ signalling.
2013,
Pubmed
,
Xenbase
Bell,
Cell fate specification and competence by Coco, a maternal BMP, TGFbeta and Wnt inhibitor.
2003,
Pubmed
,
Xenbase
Bradley,
Positive and negative signals modulate formation of the Xenopus cement gland.
1996,
Pubmed
,
Xenbase
De Robertis,
Dorsal-ventral patterning and neural induction in Xenopus embryos.
2004,
Pubmed
,
Xenbase
Gao,
The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites.
2012,
Pubmed
Hama,
The molecular basis of Src kinase specificity during vertebrate mesoderm formation.
2002,
Pubmed
,
Xenbase
Hashimoto,
The Cerberus/Dan-family protein Charon is a negative regulator of Nodal signaling during left-right patterning in zebrafish.
2004,
Pubmed
,
Xenbase
Hemmati-Brivanlou,
Inhibition of activin receptor signaling promotes neuralization in Xenopus.
1994,
Pubmed
,
Xenbase
Hsu,
The Xenopus dorsalizing factor Gremlin identifies a novel family of secreted proteins that antagonize BMP activities.
1998,
Pubmed
,
Xenbase
James,
Contribution of human embryonic stem cells to mouse blastocysts.
2006,
Pubmed
Katagiri,
Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage.
1994,
Pubmed
Kollias,
Smad7 promotes and enhances skeletal muscle differentiation.
2006,
Pubmed
Lacoste,
An efficient and reversible transposable system for gene delivery and lineage-specific differentiation in human embryonic stem cells.
2009,
Pubmed
Marques,
The activity of the Nodal antagonist Cerl-2 in the mouse node is required for correct L/R body axis.
2004,
Pubmed
Massagué,
TGFβ signalling in context.
2012,
Pubmed
Pearce,
A mouse cerberus/Dan-related gene family.
1999,
Pubmed
,
Xenbase
Schmierer,
TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.
2007,
Pubmed
Sorre,
Encoding of temporal signals by the TGF-β pathway and implications for embryonic patterning.
2014,
Pubmed
Vonica,
The left-right axis is regulated by the interplay of Coco, Xnr1 and derrière in Xenopus embryos.
2007,
Pubmed
,
Xenbase
Warmflash,
Dynamics of TGF-β signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4.
2012,
Pubmed
,
Xenbase
Wilson,
Induction of epidermis and inhibition of neural fate by Bmp-4.
1995,
Pubmed
,
Xenbase
Wu,
Tgf-beta superfamily signaling in embryonic development and homeostasis.
2009,
Pubmed
