期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：10
页码：5991-5996
DOI：10.1073/pnas.1035902100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：The NF-{kappa}B-like transcription factor Relish plays a central role in the innate immune response of Drosophila. Unlike other NF-{kappa}B proteins, Relish is activated by endoproteolytic cleavage to generate a DNA-binding Rel homology domain and a stable I{kappa}B-like fragment. This signal-induced endoproteolysis requires the activity of several gene products, including the I{kappa}B 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 I{kappa}B-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 I{kappa}B kinase {beta}. Finally, an N-terminal serine-rich region in Relish and the PEST domain were found to negatively regulate Relish activation.
