Activation of the Drosophila NF-kappa B factor Relish by rapid endoproteolytic cleavage

The Rel/NF-kappaB transcription factor Relish plays a key role in the humor al immune response in Drosophila. We now find that activation of this innat e immune response is preceded by rapid proteolytic cleavage of Relish into two parts. An N-terminal fragment, containing the DNA-binding Rel homology domain, translocates to the nucleus where it binds to the promoter of the C ecropin A1 gene and probably to the promoters of other antimicrobial peptid e genes. The C-terminal I kappa -B-like fragment remains in the cytoplasm. This endoproteolytic cleavage does not involve the proteasome, requires the DREDD caspase, and is different from previously described mechanisms for R el factor activation.