The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR–IL-1R by controlling degradation of regnase-1
H Iwasaki, O Takeuchi, S Teraguchi, K Matsushita… - Nature …, 2011 - nature.com
H Iwasaki, O Takeuchi, S Teraguchi, K Matsushita, T Uehata, K Kuniyoshi, T Satoh, T Saitoh…
Nature immunology, 2011•nature.comToll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB)
kinase (IKK) complex, which governs NF-κB-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 …
kinase (IKK) complex, which governs NF-κB-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 …
Abstract
Toll-like receptor (TLR) signaling activates the inhibitor of transcription factor NF-κB (IκB) kinase (IKK) complex, which governs NF-κB-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 IκBα, thereby activating transcription, but also regnase-1, thereby releasing a 'brake' on IL-6 mRNA expression.
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