Roles of the NF-κB Pathway in B-Lymphocyte Biology.
NF-κB was originally identified as a family of transcription factors that bind the enhancer of the immunoglobulin κ light-chain gene. Although its function in the regulation of immunoglobulin κ light-chain gene remains unclear, NF-κB plays critical roles in development, survival, and activation of B lymphocytes. In B cells, many receptors, including B-cell antigen receptor (BCR), activate NF-κB pathway, and the molecular mechanism of receptor-mediated activation of IκB kinase (IKK) complex has been partially revealed. In addition to normal B lymphocytes, NF-κB is also involved in the growth of some types of B-cell lymphomas, and many oncogenic mutations involved in constitutive activation of the NF-κB pathway were recently identified in such cancers. In this review, we first summarize the function of NF-κB in B-cell development and activation, and then describe recent progress in understanding the molecular mechanism of receptor-mediated activation of the IKK complex, focusing on the roles of the ubiquitin system. In the last section, we describe oncogenic mutations that induce NF-κB activation in B-cell lymphoma.
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan. yoshisasaki@mcp.med.kyoto-u.ac.jp.
Yoshiteru
Y
Sasaki
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
Kazuhiro
K
Iwai
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D051550:I-kappa B Kinase