Caspase-mediated processing of the Drosophila NF-kappaB factor Relish
Department of Medicine, Division of Infectious Diseases and Immunology
Animals; Base Sequence; Caspases; Cells, Cultured; Chloramphenicol O-Acetyltransferase; DNA Primers; Drosophila Proteins; Drosophila melanogaster; Gene Deletion; Gene Expression Regulation; Genes, Reporter; Kinetics; Molecular Sequence Data; Phosphorylation; Polymerase Chain Reaction; Sequence Deletion; Transcription Factors; beta-Galactosidase
Immunology and Infectious Disease
The NF-kappaB-like transcription factor Relish plays a central role in the innate immune response of Drosophila. Unlike other NF-kappaB proteins, Relish is activated by endoproteolytic cleavage to generate a DNA-binding Rel homology domain and a stable IkappaB-like fragment. This signal-induced endoproteolysis requires the activity of several gene products, including the IkappaB kinase complex and the caspase Dredd. Here we used mutational analysis and protein microsequencing to demonstrate that a caspase target site, located in the linker region between the Rel and the IkappaB-like domain, is the site of signal-dependent cleavage. We also show physical interaction between Relish and Dredd, suggesting that Dredd indeed is the Relish endoprotease. In addition to the caspase target site, the C-terminal 107 aa of Relish are required for endoproteolysis and signal-dependent phosphorylation by the Drosophila IkappaB kinase beta. Finally, an N-terminal serine-rich region in Relish and the PEST domain were found to negatively regulate Relish activation.
DOI of Published Version
Proc Natl Acad Sci U S A. 2003 May 13;100(10):5991-6. Epub 2003 May 5. Link to article on publisher's site
Proceedings of the National Academy of Sciences of the United States of America
Stoven, Svenja; Silverman, Neal S.; Junell, Anna; Hedengren-Olcott, Marika; Erturk Hasdemir, Deniz; Engstrom, Ylva; Maniatis, Tom; and Hultmark, Dan, "Caspase-mediated processing of the Drosophila NF-kappaB factor Relish" (2003). Infectious Diseases and Immunology Publications and Presentations. 15.