@article{fff1069e2f2c46b1b97ce532315668ac,
title = "The IκB kinase complex is a regulator of mRNA stability",
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 = "EDC4, IKK, P bodies, RNA stability, post-transcriptional regulation",
author = "Nadine Mikuda and Marina Kolesnichenko and Patrick Beaudette and Oliver Popp and Bora Uyar and Wei Sun and Tufan, {Ahmet Bugra} and Bj{\"o}rn Perder and Altuna Akalin and Wei Chen and Philipp Mertins and Gunnar Dittmar and Michael Hinz and Claus Scheidereit",
note = "Funding Information: We are grateful to Sabine Jungmann and Lynn Krueger for excellent technical assistance. We would like to thank Markus Landthaler for HEK cells bearing inducible HA-DDX6 vector, Elisa Izaurralde for HA-EDC4 constructs and Antje Hirsekorn/Uwe Ohler laboratory, for pEZX-MT01 plasmids. We thank Jana Wolf and Mireya Plass P{\'o}rtulas for helpful discussion and suggestions. This work was supported in part by funding from German Federal Ministry of Education and Research (BMBF) as part of the RNA Bioinformatics Center of the German Network for Bioinformatics Infrastructure (de.NBI) [031 A538C RBC (de.NBI)] to BU, from DFG (HI 1549/1-1 and SCHE 277/8-1) to MH and CS and from BMBF, CancerSys (ProSiTu) to CS. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = dec,
day = "14",
doi = "10.15252/embj.201798658",
language = "English",
volume = "37",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "24",
}