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

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 Immunol

journal_title

Nature immunology

authors

Iwasaki H,Takeuchi O,Teraguchi S,Matsushita K,Uehata T,Kuniyoshi K,Satoh T,Saitoh T,Matsushita M,Standley DM,Akira S

doi

10.1038/ni.2137

subject

Has Abstract

pub_date

2011-10-30 00:00:00

pages

1167-75

issue

12

eissn

1529-2908

issn

1529-2916

pii

ni.2137

journal_volume

12

pub_type

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