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

被引：232

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

页码：1167 / U57

页数：11

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