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The IκB kinase complex is a regulator of mRNA stability

Item Type:Article
Title:The IκB kinase complex is a regulator of mRNA stability
Creators Name:Mikuda, N. and Kolesnichenko, M. and Beaudette, P. and Popp, O. and Uyar, B. and Sun, W. and Tufan, A.B. and Perder, B. and Akalin, A. and Chen, W. and Mertins, P. and Dittmar, G. and Hinz, M. and Scheidereit, C.
Abstract:The IκB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-κB. However, we show here that IKK additionally regulates gene expression on post-transcriptional level. IKK interacted with several mRNA-binding proteins, including a Processing (P) body scaffold protein, termed enhancer of decapping 4 (EDC4). IKK bound to and phosphorylated EDC4 in a stimulus-sensitive manner, leading to co-recruitment of P body components, mRNA decapping proteins 1a and 2 (DCP1a and DCP2) and to an increase in P body numbers. Using RNA sequencing, we identified scores of transcripts whose stability was regulated via the IKK-EDC4 axis. Strikingly, in the absence of stimulus, IKK-EDC4 promoted destabilization of pro-inflammatory cytokines and regulators of apoptosis. Our findings expand the reach of IKK beyond its canonical role as a regulator of transcription.
Keywords:Endoribonucleases, HEK293 Cells, Hep G2 Cells, I-kappa B Kinase, Messenger RNA, Multiprotein Complexes, Proteins, RNA Stability, Trans-Activators
Source:EMBO Journal
Publisher:EMBO Press / Wiley
Page Range:e98658
Date:14 December 2018
Official Publication:https://doi.org/10.15252/embj.201798658
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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