Post-translational control of NF-κB signaling by ubiquitination

The transcription factor nuclear factor-kappa B (NF-kappa B) controls a number of essential cellular functions, including the immune response, cell proliferation, and apoptosis. NF-kappa B signaling must be engaged temporally and spatially and well orchestrated to prevent aberrant activation because loss of normal regulation of NF-kappa B is a major contributor to a variety of pathological diseases, including inflammatory diseases, autoimmune diseases, and cancers. Thus, understanding the molecular mechanisms controlling NF-kappa B activation is an important part of treatment of these relevant diseases. Although NF-kappa B transcriptional activity is largely regulated by nuclear translocation, post-translational modification of NF-kappa B signaling components, including phosphorylation, ubiquitination, acetylation, and methylation, has emerged as an important mechanism affecting activity. Many proteins have been shown to ubiquitinate and regulate NF-kappa B activation at the receptor signaling complex in response to a variety of ligands, such as tumor necrosis factor, interleukin-1, and Toll-like receptor ligands. In this review, we discuss our current knowledge of ubiquitination patterns and their functional role in NF-kappa B regulation.