Description
The IkB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-kB. However, we show here that IKK additionally regulates gene expression on post-transcriptional level. IKK interacted with several mRNA binding proteins, including a (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.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: EDC4, IKK, P-bodies, Posttranscriptional Regulation, RNA stability
Contact
Principal Investigators:
(in alphabetical order)
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Claus Scheidereit, MDC, Germany
Nadine Mikuda, MDC, Germany
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proteolli
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