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Smoothened transduces Hedgehog signal by forming a complex with Evc/Evc2
Update time:2012-09-24  |  Author:  |   【Print】【Close】

Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis in species ranging from Drosophila to mammals. Malfunction of this pathway has been implicated in numerous human disorders including congenital anomalies and cancers, such as basal cell carcinoma, Medulloblastoma, lung cancer, liver cancer, etc. The Hh signaling is transduced by Smoothened (Smo), a seven-transmembrane protein related to G protein coupled receptors (GPCRs). Despite a conserved mechanism by which Hh activates Smo in Drosophila and mammals, how mammalian Hh signal is transduced from Smo to the Gli transcription factors is poorly understood.

Dr. Yongbin Chen and his team recently provided evidence that two ciliary proteins, Evc and Evc2, the products of human disease genes responsible for the Ellis-van Creveld syndrome, act downstream of Smo to transduce the Hh signal while act upstream of Sufu to promote Gli activation. Furthermore, they demonstrated that Hh stimulates binding of Evc/Evc2 to Smo depending on phosphorylation of Smo C-terminal intracellular tail, which recruits Evc/Evc2 to activate Gli proteins by antagonizing Sufu in the primary cilia.

These results have been published by Cell Research on Sep 18th, 2012 (doi: 10.1038/cr.2012.134). Dr. Yongbin Chen is supported by grants from Chinese Academy of Sciences, the National Natural Science Foundation of China,National Key Basic Research Program, and American Heart Association Postdoctoral Fellowship.


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