| 摘 要： | 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,ccdcl36 a and ccdc136 b,but only ccdc136 b is highly expressed during early embryonic development.In this study,we demonstrate that ccdc136 b is required for dorsal-ventral axial patterning in zebrafish embryos.ccdc136 b morphants display strongly dorsalized phenotypes.Loss- and gain-of-function experiments in zebrafish embryos and mammalian cells show that Ccdc136 b 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 Ccdc136 b 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.
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