The nuclear signaling of NF-kappaB: current knowledge, new insights, and future perspectives.
The 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.
Wan
Fengyi
F
Laborathory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. fwan@niaid.nih.gov
Lenardo
Michael J
MJ
D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
D016328:NF-kappa B; D009687:Nuclear Proteins; D021122:Protein Subunits; C031016:RPS3A protein, human; D012269:Ribosomal Proteins; D014157:Transcription Factors