The COP9 signalosome regulates multiple pleiotropic pathways in Drosophila melanogaster.

The COP9 signalosome (CSN) is an essential eight-subunit repressor of light-regulated development in Arabidopsis. This complex has also been identified in mammals, though its role
remains obscure. Among the subunits of the CSN are Jab1 (COP9 Signalosome subunit 5, CSN5), a c-Jun coactivator, CSN1, a Ga pathway suppressor, and TRIP15/CSN2, a thyroid-hormone receptor binding protein. These subunits have roles in various cellular processes, suggesting a possible role for the CSN as an integrator of multiple signaling pathways. To elucidate the function of the CSN
in animals, a Drosophila model system has been established. Gel-filtration analysis with antibodies against the subunits revealed that these proteins act as a complex in Drosophila that is similar in size to the plant and mammalian complexes. Null mutations in one of two subunits, Csn4 and Csn5, are larval lethal. Successful embryogenesis appears to be a consequence of maternal contribution of the complex. Phenotypic characterization of these two mutants indicates that this lethality probably results from numerous pleiotropic effects, including defects in cell-cycle regulation and hematopoesis. Interestingly, while some of the phenotypes are shared between the two mutants, each mutant also has unique phenotypes, which suggest specific roles for each subunit. Biochemical analysis indicates that the different subunits are found in both CSN-dependent and CSN-independent forms and that these forms are differentially affected by the mutations.