Caspase-mediated processing of the Drosophila NF-κB factor Relish

被引:263
作者
Stöven, S
Silverman, N
Junell, A
Hedengren-Olcott, M
Erturk, D
Engström, Y
Maniatis, T
Hultmark, D
机构
[1] Umea Univ, Umea Ctr Mol Pathogenesis, S-90187 Umea, Sweden
[2] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA
[3] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
[4] Stockholm Univ, Dept Mol Biol & Funct Genom, S-10691 Stockholm, Sweden
[5] Stockholm Univ, Wenner Gren Inst, S-10691 Stockholm, Sweden
关键词
D O I
10.1073/pnas.1035902100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 ReI 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 ReI 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.
引用
收藏
页码:5991 / 5996
页数:6
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