The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1

被引：226
作者：
Iwasaki, Hidenori [1 ,2 ]
Takeuchi, Osamu [1 ,3 ]
Teraguchi, Shunsuke [1 ,4 ]
Matsushita, Kazufumi [1 ]
Uehata, Takuya [1 ,5 ]
Kuniyoshi, Kanako [1 ,3 ]
Satoh, Takashi [1 ]
Saitoh, Tatsuya [1 ,3 ]
Matsushita, Mutsuyoshi [2 ]
Standley, Daron M. [4 ]
Akira, Shizuo [1 ,3 ]
机构：
[1] Osaka Univ, Host Def Lab, World Premier Int Immunol Frontier Res Ctr, Osaka, Japan
[2] Cent Pharmaceut Res Inst, Osaka, Japan
[3] Osaka Univ, Microbial Dis Res Inst, Osaka, Japan
[4] Osaka Univ, Lab Syst Immunol, World Premier Int Immunol Frontier Res Ctr, Osaka, Japan
[5] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Osaka, Japan
来源：
NATURE IMMUNOLOGY | 2011年 / 12卷 / 12期
基金：
日本学术振兴会;
关键词：
POSTTRANSCRIPTIONAL CONTROL; ALPHA PRODUCTION; BETA-TRCP; ACTIVATION; UBIQUITIN; PHOSPHORYLATION; INFLAMMATION; RECOGNITION; NEMO; INDUCTION;
D O I：
10.1038/ni.2137
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-kappa B (I kappa B) kinase (IKK) complex, which governs NF-kappa B-mediated transcription during inflammation. The RNase regnase-1 serves a critical role in preventing autoimmunity by controlling the stability of mRNAs that encode cytokines. Here we show that the IKK complex controlled the stability of mRNA for interleukin 6 (IL-6) by phosphorylating regnase-1 in response to stimulation via the IL-1 receptor (IL-1R) or TLR. Phosphorylated regnase-1 underwent ubiquitination and degradation. Regnase-1 was reexpressed in IL-1R- or TLR-activated cells after a period of lower expression. Regnase-1 mRNA was negatively regulated by regnase-1 itself via a stem-loop region present in the regnase-1 3' untranslated region. Our data demonstrate that the IKK complex phosphorylates not only I kappa B alpha, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression.
引用
收藏
页码：1167 / U57
页数：11
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