Coco is a dual activity modulator of TGFβ signaling
- Development. 2015 Aug 1;142(15):2678-85. doi: 10.1242/dev.122358.
- 1. Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA.
- 2. Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA Laboratory of Theoretical Condensed Matter Physics, The Rockefeller University, New York, NY 10065, USA.
- 3. Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA [email protected].
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.