Coco is a dual activity modulator of TGFβ signaling

Development. 2015 Aug 1;142(15):2678-85. doi: 10.1242/dev.122358. Epub 2015 Jun 26.


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.

Keywords: Coco; Dual-activity pathway modulators; TGFβ signaling modulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA Primers / genetics
  • Fluorescent Antibody Technique
  • Immunoprecipitation
  • Luciferases
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta1 / metabolism*
  • Xenopus / metabolism*
  • Xenopus Proteins / metabolism*


  • DAND5 protein, Xenopus
  • DNA Primers
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Xenopus Proteins
  • Luciferases
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I