title: The coiled-coil domain containing protein Ccdc136b antagonizes maternal Wnt/β-catenin activity during zebrafish dorsoventral axial patterning.
abstract: The coiled-coil domain containing protein CCDC136 is a putative tumor suppressor and significantly down-regulated in gastric and colorectal cancer tissues. However, little is known about its biological functions during vertebrate embryo development. Zebrafish has two CCDC136 orthologs, ccdc136a and ccdc136b, but only ccdc136b is highly expressed during early embryonic development. In this study, we demonstrate that ccdc136b is required for dorsal-ventral axial patterning in zebrafish embryos. ccdc136b morphants display strongly dorsalized phenotypes. Loss- and gain-of-function experiments in zebrafish embryos and mammalian cells show that Ccdc136b is a crucial negative regulator of the Wnt/β-catenin signaling pathway, and plays a critical role in the establishment of the dorsal-ventral axis. We further find that Ccdc136b interacts with APC, promotes the binding affinity of APC with β-catenin and then facilitates the turnover of β-catenin. These results provide the first evidence that CCDC136 regulates zebrafish dorsal-ventral patterning by antagonizing Wnt/β-catenin signal transduction and suggest a potential mechanism underlying its suppressive activity in carcinogenesis.
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hanqiao
authors.initials: H
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Membrane Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: qiangwang@ioz.ac.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D009035:Mothers; D059748:Proteolysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C000624215:Ccdc136b protein, zebrafish; D025521:Tumor Suppressor Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
keywords: CCDC136; Dorsal-ventral patterning; Wnt signaling; Zebrafish; β-catenin