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The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives Wan F; Lenardo MJCell Res 2010[Jan]; 20 (1): 24-33The nuclear factor-kappa B (NF-kappaB) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-kappaB is normally sequestered in the cytoplasm by a family of inhibitory proteins known as inhibitors of NF-kappaB (IkappaBs). The signal pathways leading to the liberation and nuclear accumulation of NF-kappaB, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-kappaB must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-kappaB transcriptional activity. A non-Rel subunit of NF-kappaB, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-kappaB, including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-kappaB in the nucleus. Further insights into the nuclear events that govern NF-kappaB function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-kappaB-associated diseases.|Animals[MESH]|Cell Nucleus/*genetics[MESH]|Humans[MESH]|Immunity/*genetics[MESH]|Inflammation/*genetics[MESH]|NF-kappa B/*metabolism[MESH]|Nuclear Proteins/genetics[MESH]|Protein Subunits/genetics[MESH]|Ribosomal Proteins/genetics[MESH]|Signal Transduction/*genetics/immunology[MESH]|Transcription Factors/genetics[MESH]|Transcriptional Activation/genetics[MESH] |
