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XB-ART-36192
EMBO J 2007 Aug 08;2615:3592-606. doi: 10.1038/sj.emboj.7601781.
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XRab40 and XCullin5 form a ubiquitin ligase complex essential for the noncanonical Wnt pathway.

Lee RH, Iioka H, Ohashi M, Iemura S, Natsume T, Kinoshita N.


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Rab GTPases are key regulators of intracellular membrane trafficking. We sought to elucidate the roles of Rab GTPases in Xenopus gastrulation, and found that a Xenopus homolog of Rab40 (XRab40) is required for normal gastrulation. XRab40 is localized at the Golgi apparatus and interacts with ElonginB/C and Cullin5 to form a ubiquitin ligase. XRab40/XCullin5 functions cooperatively and regulates the ubiquitination and localization of Rap2 GTPase. Furthermore, XRab40/XCullin5 regulates the membrane localization of Dishevelled (Dsh), a key signaling molecule in the Wnt pathway, through Rap2 and its effector Misshapen/Nck-interacting kinase (XMINK). XMINK interacts with Dsh, and is translocated to the plasma membrane by Wnt activation. We propose a novel signaling cascade consisting of XRab40/XCullin5, Rap2 and XMINK, which plays a crucial role in the regulation of the noncanonical Wnt pathway.

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Species referenced: Xenopus
Genes referenced: cul5 dvl1 dvl2 elob kcne1 mink1 nck1 rab40b rab40c rap2a
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References [+] :
Angers, The KLHL12-Cullin-3 ubiquitin ligase negatively regulates the Wnt-beta-catenin pathway by targeting Dishevelled for degradation. 2006, Pubmed, Xenbase