title: Inhibition of the nuclear import of cubitus interruptus by roadkill in the presence of strong hedgehog signal.
abstract: Hedgehog (Hh) signalling plays an important role in various developmental processes by activating the Cubitus interruptus (Ci)/Glioblastoma (Gli) family of transcription factors. In the process of proper pattern formation, Ci activity is regulated by multiple mechanisms, including processing, trafficking, and degradation. However, it remains elusive how Ci distinctly recognizes the strong and moderate Hh signals. Roadkill (Rdx) induces Ci degradation in the anterior region of the Drosophila wing disc. Here, we report that Rdx inhibited Ci activity by two different mechanisms. In the region abutting the anterior/posterior boundary, which receives strong Hh signal, Rdx inhibited the nuclear import of Ci by releasing importin α3 from Ci. In this region, Rdx negatively regulated the expression of transcription factor Knot/Collier. In farther anterior regions receiving moderate levels of Hh signal, Rdx induced Ci degradation, as reported previously. Thus, two different mechanisms by which Rdx negatively regulates Ci may play an important role in the fine-tuning of Hh responses.
authors.affiliation: Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Japan.
authors.forename: Ki-Hyeon
authors.initials: KH
authors.lastname: Seong
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akimaru
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.forename: Teruaki
authors.initials: T
authors.lastname: Nomura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okada
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ishii
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005838:Genotype; D053823:Hedgehog Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D020033:Protein Isoforms; D034622:RNA Interference; D014157:Transcription Factors / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020033:Protein Isoforms; C511791:Rdx protein, Drosophila; D014157:Transcription Factors; C092937:ci protein, Drosophila