Caspase-mediated processing of the Drosophila NF-kappaB factor Relish.
2003 (English)In: Proc Natl Acad Sci U S A, ISSN 0027-8424, Vol. 100, no 10, 5991-6 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 100, no 10, 5991-6 p.
Animals, Base Sequence, Caspases/*metabolism, Cells; Cultured, Chloramphenicol O-Acetyltransferase/genetics, DNA Primers, Drosophila Proteins/*genetics/metabolism, Drosophila melanogaster/*immunology, Gene Deletion, Gene Expression Regulation, Genes; Reporter, Kinetics, Molecular Sequence Data, Phosphorylation, Polymerase Chain Reaction, Sequence Deletion, Transcription Factors/*genetics/metabolism, beta-Galactosidase/genetics
IdentifiersURN: urn:nbn:se:umu:diva-17059PubMedID: 12732719OAI: oai:DiVA.org:umu-17059DiVA: diva2:156732