title: Members of the Rusc protein family interact with Sufu and inhibit vertebrate Hedgehog signaling.
abstract: Hedgehog (Hh) signaling is fundamentally important for development and adult tissue homeostasis. It is well established that in vertebrates Sufu directly binds and inhibits Gli proteins, the downstream mediators of Hh signaling. However, it is unclear how the inhibitory function of Sufu towards Gli is regulated. Here we report that the Rusc family of proteins, the biological functions of which are poorly understood, form a heterotrimeric complex with Sufu and Gli. Upon Hh signaling, Rusc is displaced from this complex, followed by dissociation of Gli from Sufu. In mammalian fibroblast cells, knockdown of Rusc2 potentiates Hh signaling by accelerating signaling-induced dissociation of the Sufu-Gli protein complexes. In Xenopus embryos, knockdown of Rusc1 or overexpression of a dominant-negative Rusc enhances Hh signaling during eye development, leading to severe eye defects. Our study thus uncovers a novel regulatory mechanism controlling the response of cells to Hh signaling in vertebrates.
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Schwend
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, IL 61802, USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Mei
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001 S Lincoln Avenue, Urbana, IL 61802, USA yangj@illinois.edu.
authors.forename: Jing
authors.identifier: 0000-0002-4983-1660
authors.initials: J
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D005810:Multigene Family; D041681:NIH 3T3 Cells; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C568067:Sufu protein, Xenopus; D029867:Xenopus Proteins
keywords: Gli; Hedgehog signaling; Human; Mouse; Rusc; Sufu; Xenopus