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The IκB kinase complex is a regulator of mRNA stability
Author(s) -
Mikuda Nadine,
Kolesnichenko Marina,
Beaudette Patrick,
Popp Oliver,
Uyar Bora,
Sun Wei,
Tufan Ahmet Bugra,
Perder Björn,
Akalin Altuna,
Chen Wei,
Mertins Philipp,
Dittmar Gunnar,
Hinz Michael,
Scheidereit Claus
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201798658
Subject(s) - molecular medicine , center (category theory) , biology , library science , computational biology , gene , genetics , computer science , chemistry , cell cycle , crystallography
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 ( EDC 4). IKK bound to and phosphorylated EDC 4 in a stimulus‐sensitive manner, leading to co‐recruitment of P body components, mRNA decapping proteins 1a and 2 ( DCP 1a and DCP 2) and to an increase in P body numbers. Using RNA sequencing, we identified scores of transcripts whose stability was regulated via the IKK ‐ EDC 4 axis. Strikingly, in the absence of stimulus, IKK ‐ EDC 4 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.