Nuclear localization of the Drosophila IκB protein Cactus and its response to the Toll signaling pathway
(English)Manuscript (preprint) (Other academic)
In Drosophila, the Toll signaling pathway is known as a regulator of both dorso-ventral patterning during embryogenesis and regulation of immunity. Activation of of the Toll pathway results in nuclear accumulation of the NFκB/Rel transcription factors Dif and Dorsal, and the subsequent activation of downstream target genes. The current model is that Cactus is a strictly cytoplasmic protein, interacting with Dorsal and Dif to inhibit their nuclear translocation. However, immunostaining revealed that Cactus is present both in the nucleus and cytoplasm of fat body cells and S2 cells. Activation of Toll signaling in cell culture demonstrated that a nuclear form of Cactus is stable and persists during signaling, while cytoplasmic Cactus is degraded in a proteosome-dependent manner and then re-synthesized. Alternative splicing of Cactus pre-mRNA produces two Cactus isoforms, differing by 18 amino acids in the C-terminus. We show that both isoforms act as inhibotors of Dif- and Dorsal-mediated Drosomycin-luciferase expression, although the longer isoform of Cactus was a slightly better inhibitor. Both isoforms showed similar subcellular distribution, being present both in the cytoplasm and nucleus of larval fat body cells. Thus, the present finding suggest that Cactus does not act as a degradeable, cytoplasmic inhibitor of Dif and Dorsal, but also plays a role in the nucleus during immune challenge.
Research subject Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-64254OAI: oai:DiVA.org:su-64254DiVA: diva2:456477