The IκB kinase complex is a regulator of mRNA stability

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Item Type:	Article
Title:	The IκB kinase complex is a regulator of mRNA stability
Creators Name:	Mikuda, N., Kolesnichenko, M., Beaudette, P., Popp, O., Uyar, B., Sun, W., Tufan, A.B., Perder, B., Akalin, A., Chen, W., Mertins, P., Dittmar, G., 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
ISSN:	0261-4189
Publisher:	EMBO Press / Wiley
Volume:	37
Number:	24
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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