The IκB kinase complex is a regulator of mRNA stability


  • N. Mikuda
  • M. Kolesnichenko
  • P. Beaudette
  • O. Popp
  • B. Uyar
  • W. Sun
  • A.B. Tufan
  • B. Perder
  • A. Akalin
  • W. Chen
  • P. Mertins
  • G. Dittmar
  • M. Hinz
  • C. Scheidereit


  • EMBO Journal


  • EMBO J 37 (24): e98658


  • 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.