title: Regulation of Ci and Su(fu) nuclear import in Drosophila.
abstract: The Hedgehog (Hh) signal transduction pathway plays a central role in the development of invertebrates and vertebrates. While much is known about the pathway, the role of Suppressor of fused (Su(fu)), a component of the pathway's signaling complex has remained enigmatic. Previous studies have linked Su(fu) to the cytoplasmic sequestration of the zinc finger transcription factor, Cubitus interruptus (Ci), while other studies suggest a role in modulating target gene expression. In examining the cell biology of the pathway, we have found that like its vertebrate homologue, Drosophila Su(fu) enters the nucleus. Furthermore, we find that the nuclear import of Su(fu) occurs in concert with that of Ci in response to Hh signaling. Here, we examine the mechanism by which Su(fu) regulates Ci import by investigating the importance of the Ci nuclear localization signal (NLS) and the effect of adding an additional NLS. Finally, we demonstrate that Ci can bring Su(fu) with it to a multimerized Ci DNA binding site. These results provide a basis for understanding the dual roles played by Su(fu) in the regulation of Ci.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Sisson
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Ziegenhorn
authors.forename: Robert A
authors.initials: RA
authors.lastname: Holmgren
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D053823:Hedgehog Proteins; D019913:Nuclear Localization Signals; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019913:Nuclear Localization Signals; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; D014157:Transcription Factors; C092937:ci protein, Drosophila; C077245:hh protein, Drosophila