Victoria H Ng, Zachary Spencer, Leif R Neitzel, Anmada Nayak, Matthew A Loberg, Chen Shen, Sara N Kassel, Heather K Kroh, Zhenyi An, Christin C Anthony, Jamal M Bryant, Amanda Lawson, Lily Goldsmith, Hassina Benchabane, Amanda G Hansen, Jingjing Li, Starina D'Souza, Andres M Lebensohn, Rajat Rohatgi, William A Weiss, Vivian L Weiss, Charles Williams, Charles C Hong, David J Robbins, Yashi Ahmed, Ethan Lee
The relative abundance of Wnt receptors plays a crucial role in controlling Wnt signaling in tissue homeostasis and human disease. While the ubiquitin ligases that ubiquitylate Wnt receptors are well-characterized, the deubiquitylase that reverses these reactions remains unclear. Herein, we identify USP46, UAF1, and WDR20 (USP46 complex) as positive regulators of Wnt signaling in cultured human cells. We find that the USP46 complex is similarly required for Wnt signaling in Xenopus and zebrafish embryos. We demonstrate that Wnt signaling promotes the association between the USP46 complex and cell surface Wnt coreceptor, LRP6...
October 5, 2023: Nature Communications