Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway

The diverse cellular and biological functions of the nuclear factor kappa B (NF-kappa B) pathway, together with the catastrophic consequences of its aberrant regulation, demand specific and highly regulated control of its activity. As described in this review, regulation of the NF-kappa B pathway is brought about through multiple post-translational modi. cations that control the activity of the core components of NF-kappa B signaling: the I kappa B kinase (IKK) complex, the I kappa B proteins and the NF-kappa B subunits themselves. These regulatory modi. cations, which include phosphorylation, ubiquitination, acetylation, sumoylation and nitrosylation, can vary, depending on the nature of the NF-kappa B-inducing stimulus. Moreover, they frequently have distinct, sometimes antagonistic, functional consequences and the same modi. cation can have different effects depending on the context. Given the important role of NF-kappa B in human health and disease, understanding these pathways will not only provide valuable insights into mechanism and function, but could also lead to new drug targets and the development of diagnostic and prognostic biomarkers for many pathological conditions.