Molecular mechanisms in lymphocyte activation and growth.
Transcription factor NF-kappaB is biochemically coupled to the T cell antigen receptor (TCR) and activated transiently during an adaptive immune response. The author's laboratory is investigating the signal-dependent regulation of NF-kappaB, its downstream gene targets, and its function in lymphocyte biology. Our studies have revealed novel enzymatic checkpoints in the NF-kappaB signaling pathway and constitutive repressors of NF-kappaB that might be clinically applicable for therapeutic control of the immune system. We have also found that the Tax transforming protein encoded by human T cell leukemia virus type 1 (HTLV1) binds to and persistently activates an inducible protein kinase in the TCR/NF-kappaB axis. This viral/host interaction appears to trigger the inappropriate expression of NF-kappaB and the development of HTLV1-associated disease.
Ballard
D W
DW
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232-0295, USA. dean.ballard@mcmail.vanderbilt.edu
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002453:Cell Cycle; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D004790:Enzyme Induction; D005786:Gene Expression Regulation; D016356:Gene Products, tax / Q000502:physiology; D006678:HIV / Q000502:physiology; D015490:HTLV-I Infections / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000502:physiology*; D046911:Macromolecular Substances; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D015202:Protein Engineering; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D016356:Gene Products, tax; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007376:Interleukin-2; D046911:Macromolecular Substances; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D015375:Receptors, Interleukin-2; D000072000:NF-KappaB Inhibitor alpha