title: COP9 signalosome subunit 5 (CSN5/Jab1) regulates the development of the Drosophila immune system: effects on Cactus, Dorsal and hematopoiesis.
abstract: The COP9 signalosome is a multifunctional regulator essential for Drosophila development. A loss-of-function mutant in Drosophila COP9 signalosome subunit 5 (CSN5) develops melanotic bodies, a phenotype common to mutants in immune signaling. csn5(null) larvae accumulated high levels of Cactus that co-localizes with Dorsal to the nucleus. However, Dorsal-dependent transcriptional activity remained repressed in the absence of an inducing signal, despite its nuclear localization. Dorsal activity in mutant larvae and NFkappaB activity in CSN5 down-regulated mammalian cells can be induced following activation of the Toll/IL-1 pathway. csn5(null) larvae contained more hemocytes than wild-type (wt) larvae. A large portion of these cells have differentiated to lamellocytes (LM), a hemocyte cell type rarely seen in normal larvae. The results presented here indicate that CSN5 is a negative regulator of Dorsal subcellular localization, and of hemocyte proliferation and differentiation. These results further indicate that nuclear localization of Dorsal can be uncoupled from its activation. Surprisingly, CSN5 is not necessary for immune-induced degradation of Cactus.
authors.affiliation: Department of Plant Sciences, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Harari-Steinberg
authors.forename: Rafael
authors.initials: R
authors.lastname: Cantera
authors.forename: Simona
authors.initials: S
authors.lastname: Denti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bianchi
authors.forename: Efrat
authors.initials: E
authors.lastname: Oron
authors.forename: Daniel
authors.initials: D
authors.lastname: Segal
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Chamovitz
mesh_terms: D000818:Animals; D000075686:COP9 Signalosome Complex; D004268:DNA-Binding Proteins / Q000502:physiology*; D004330:Drosophila / Q000276:immunology*; D029721:Drosophila Proteins / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D046912:Multiprotein Complexes / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D010447:Peptide Hydrolases / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; C062236:dl protein, Drosophila; C077938:cact protein, Drosophila; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex