title: Cactus-independent regulation of Dorsal nuclear import by the ventral signal.
abstract: Rel-family transcription factors function in a variety of biological processes, including development and immunity. During early Drosophila development, the Toll-Cactus-Dorsal pathway regulates the establishment of the embryonic dorsoventral axis. The last step in this pathway is the graded nuclear import of the Rel protein Dorsal. Dorsal is retained in the cytoplasm by the IkappaB-family protein Cactus. Phosphorylation of both Dorsal and Cactus is regulated by a Toll-receptor-dependent ventral signal relayed by the Tube and Pelle proteins. Phosphorylation of Cactus leads to its degradation and to the release of Dorsal to form a ventral-to-dorsal nuclear Dorsal gradient. To understand how the ventral signal regulates the nuclear import and activity of Dorsal, we deleted its conserved nuclear localization signal (NLS). The truncated protein remained in the cytoplasm and could antagonize the function of wild-type Dorsal, suggesting that Dorsal forms a dimer in the cytoplasm. Further, the nuclear import of a mutant Dorsal protein that failed to interact with Cactus was still regulated by the ventral signal. Our results are consistent with a model in which ventral signal-dependent modification of both Cactus and Dorsal is required for the graded nuclear import of Dorsal.
authors.affiliation: Waksman Institute, Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854-8020, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Drier
authors.forename: S
authors.initials: S
authors.lastname: Govind
authors.forename: R
authors.initials: R
authors.lastname: Steward
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D019281:Dimerization; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000502:physiology / Q000648:ultrastructure; D019476:Insect Proteins / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D009024:Morphogenesis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; D014157:Transcription Factors; C062236:dl protein, Drosophila; C084727:tub protein, Drosophila; C077938:cact protein, Drosophila; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases