title: Receptor for Activated C Kinase 1 (RACK1) Promotes Dishevelled Protein Degradation via Autophagy and Antagonizes Wnt Signaling.
abstract: Wnt signaling plays a critical role in embryonic development, tissue homeostasis, and cancer development. Dishevelled (Dvl) is an essential and central component in Wnt signaling, and its stability and activity is tightly regulated. It has been shown that Dvl can be degraded via both the proteasome and autophagy-lysosome pathways. Here we report that receptor for activated C kinase 1 (RACK1) negatively regulates Dishevelled stability and Wnt signaling. RACK1 interacts with Dvl proteins and promotes their lysosomal degradation, and this effect is enhanced by autophagy induction. RACK1 also interacts with LC3 and enhances the association of LC3 with Dvl2, thereby leading to degradation of Dvl proteins through autophagy. These findings reveal a novel regulatory function of RACK1 in Wnt signaling by modulating Dvl stability.
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Minzhang
authors.initials: M
authors.lastname: Cheng
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xue
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Cao
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Bofeng
authors.initials: B
authors.lastname: Liu
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Benyu
authors.initials: B
authors.lastname: Ma
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yan
authors.affiliation: From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: ygchen@tsinghua.edu.cn.
authors.forename: Ye-Guang
authors.initials: YG
authors.lastname: Chen
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism; D001343:Autophagy; D002478:Cells, Cultured; D000072261:Dishevelled Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D008247:Lysosomes / Q000378:metabolism; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D051381:Rats; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: C000606581:DVL2 protein, human; D000072261:Dishevelled Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins
keywords: Dishevelled; RACK1; Wnt signaling; autophagy; lysosome; protein degradation; protein stability