title: IQGAP1 protein regulates nuclear localization of β-catenin via importin-β5 protein in Wnt signaling.
abstract: In the canonical Wnt signaling pathway, the translocation of β-catenin is important for the activation of target genes in the nucleus. However, the molecular mechanisms underlying its nuclear localization remain unclear. In the present study, we found IQGAP1 to be a regulator of β-catenin function via importin-β5. In Xenopus embryos, depletion of IQGAP1 reduced Wnt-induced nuclear accumulation of β-catenin and expression of Wnt target genes during early embryogenesis. Depletion of endogenous importin-β5 associated with IQGAP1 also reduced expression of Wnt target genes and the nuclear localization of IQGAP1 and β-catenin. Moreover, a small GTPase, Ran1, contributes to the nuclear translocation of β-catenin and the activation of Wnt target genes. These results suggest that IQGAP1 functions as a regulator of translocation of β-catenin in the canonical Wnt signaling pathway.
authors.affiliation: From the Department of Molecular Cell Biology, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510 and.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Goto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sato
authors.forename: Shungo
authors.initials: S
authors.lastname: Adachi
authors.forename: Shun-ichiro
authors.initials: S
authors.lastname: Iemura
authors.forename: Tohru
authors.initials: T
authors.lastname: Natsume
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibuya
mesh_terms: D021581:Active Transport, Cell Nucleus; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D060449:Wnt Signaling Pathway; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*; D028961:beta Karyopherins / Q000378:metabolism*; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C107940:IPO5 protein, human; C101203:IQ motif containing GTPase activating protein 1; D010750:Phosphoproteins; D029867:Xenopus Proteins; D051176:beta Catenin; D028961:beta Karyopherins; D020703:ras GTPase-Activating Proteins; D020559:Monomeric GTP-Binding Proteins
keywords: Beta-Catenin; Dvl; IQGAP; Importin; Nuclear Translocation; Nuclear Transport; Ran; Signal Transduction; Wnt Pathway; Wnt Signaling