title: Coco is a dual activity modulator of TGFβ signaling.
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.
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Deglincerti
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Haremaki
authors.affiliation: 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.
authors.forename: Aryeh
authors.initials: A
authors.lastname: Warmflash
authors.affiliation: 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.
authors.forename: Benoit
authors.initials: B
authors.lastname: Sorre
authors.affiliation: Laboratory of Stem Cell Biology and Molecular Embryology, The Rockefeller University, New York, NY 10065, USA brvnlou@rockefeller.edu.
authors.forename: Ali H
authors.initials: AH
authors.lastname: Brivanlou
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D005455:Fluorescent Antibody Technique; D047468:Immunoprecipitation; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*
chemical_list: C473314:DAND5 protein, Xenopus; D017931:DNA Primers; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D029867:Xenopus Proteins; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: Coco; Dual-activity pathway modulators; TGFβ signaling modulators