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.
journal_name
Nat Immunoljournal_title
Nature immunologyauthors
Iwasaki H,Takeuchi O,Teraguchi S,Matsushita K,Uehata T,Kuniyoshi K,Satoh T,Saitoh T,Matsushita M,Standley DM,Akira Sdoi
10.1038/ni.2137subject
Has Abstractpub_date
2011-10-30 00:00:00pages
1167-75issue
12eissn
1529-2908issn
1529-2916pii
ni.2137journal_volume
12pub_type
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