| First Author | Iwasaki H | Year | 2011 |
| Journal | Nat Immunol | Volume | 12 |
| Issue | 12 | Pages | 1167-75 |
| PubMed ID | 22037600 | Mgi Jnum | J:179016 |
| Mgi Id | MGI:5300871 | Doi | 10.1038/ni.2137 |
| Citation | Iwasaki H, et al. (2011) The IkappaB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol 12(12):1167-75 |
| abstractText | Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-kappaB (IkappaB) kinase (IKK) complex, which governs NF-kappaB-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 IkappaBalpha, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression. |
