Regulation and function of NF-kappaB transcription factors in the immune system.
The mammalian Rel/NF-kappaB family of transcription factors, including RelA, c-Rel, RelB, NF-kappaB1 (p50 and its precursor p105), and NF-kappaB2 (p52 and its precursor p100), plays a central role in the immune system by regulating several processes ranging from the development and survival of lymphocytes and lymphoid organs to the control of immune responses and malignant transformation. The five members of the NF-kappaB family are normally kept inactive in the cytoplasm by interaction with inhibitors called IkappaBs or the unprocessed forms of NF-kappaB1 and NF-kappaB2. A wide variety of signals emanating from antigen receptors, pattern-recognition receptors, receptors for the members of TNF and IL-1 cytokine families, and others induce differential activation of NF-kappaB heterodimers. Although work over the past two decades has shed significant light on the regulation of NF-kappaB transcription factors and their functions, much progress has been made in the past two years revealing new insights into the regulation and functions of NF-kappaB. This recent progress is covered in this review.
Vallabhapurapu
Sivakumar
S
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA.
Karin
Michael
M
D000818:Animals; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007107:Immune System / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology; D022423:Myeloid Cells / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D020672:I-kappa B Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha