COP9 signalosome subunit 5 (CSN5/Jab1) regulates the development of the Drosophila immune system: Effects on Cactus, Dorsal and hematopoiesis

Orit Harari-Steinberg, Rafael Cantera, Simona Denti, Elisabetta Bianchi, Efrat Oron, Daniel Segal, Daniel A. Chamovitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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. csn5null 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 NFκB activity in CSN5 down-regulated mammalian cells can be induced following activation of the Toll/IL-1 pathway. csn5null 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.

Original languageEnglish
Pages (from-to)183-195
Number of pages13
JournalGenes to Cells
Volume12
Issue number2
DOIs
StatePublished - Feb 2007

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