Posttranslational modifications of NEMO and its partners in NF-κB signaling

NEMO, the regulatory subunit of the IκB kinase (IKK) complex that controls the activation of the transcription factor NF-κB, is required for IKK function in most situations, but its exact mode of action has remained elusive until recently. A series of publications now provides information about how posttranscriptional modifications of NEMO, such as ubiquitination, sumoylation or phosphorylation, regulate its function in the IKK complex. These modifications might also regulate a cytosolic pool of free NEMO that controls the activation of NF-κB induced by genotoxic stress. Together with a better identification of the modifications controlling partners of NEMO, a clearer picture of how IKK becomes activated upon cell stimulation is starting to emerge, providing new clues for how the NF-κB pathway could be modulated for therapeutic purposes.