More than just an IκB kinase: the IKK complex coordinates mRNA stability and transcription

Abstract

The IκB kinase (IKK) complex is best known as the core regulator of NF‐κB signalling. Recent work from Mikuda et al reveals a new and unexpected function for IKK in the regulation of mRNA stability. Through interacting with and phosphorylating EDC4, a key component of the mRNA decapping complex, IKK regulates P‐body formation and the stability of numerous mRNAs, including many encoding inflammatory cytokines. Activation of IKK can therefore be more generally thought of as programming the cellular response to stress and infection through both mRNA stability and transcription.See also: N Mikuda et al (December 2018)The EMBO Journal (2018) 37: e101084OpenUrlAbstract/FREE Full TextThe complexity of the numerous signals leading to activation of the NF‐κB transcription factor and the diversity of its roles as a regulator of gene expression can appear bewildering. However, a common feature of almost all stimuli that activate this pathway, be they inflammatory cytokines, pathogen‐associated molecular patterns (PAMPs) or cellular stresses such as DNA damage, is convergence on the IκB kinase (IKK) complex (Hinz & Scheidereit, 2014). IKK activation typically results from its proximity‐induced phosphorylation by a kinase such as transforming growth factor β‐activated kinase 1 (TAK1), facilitated through recruitment by linear and lysine 63 (K63)‐linked ubiquitin chains (Hinz & Scheidereit, 2014). In the case of IKK, this is mediated by ubiquitin binding motifs present in its regulatory subunit IKKγ (NEMO; Hinz & Scheidereit, 2014). In addition, the IKK complex contains two catalytic subunits IKKα and IKKβ. Of these, IKKβ is primarily responsible for activating the “classical” NF‐κB pathway, through phosphorylation and subsequent lysine 48 …