Molecular mechanisms in lymphocyte activation and growth

Immunol Res. 2001;23(2-3):157-66. doi: 10.1385/IR:23:2-3:157.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Cycle
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Enzyme Induction
  • Gene Expression Regulation
  • Gene Products, tax / physiology
  • HIV / physiology
  • HTLV-I Infections / immunology
  • Human T-lymphotropic virus 1 / physiology
  • Humans
  • I-kappa B Proteins*
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / genetics
  • Lymphocyte Activation / physiology*
  • Macromolecular Substances
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / physiology*
  • Protein Engineering
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / genetics
  • Signal Transduction / physiology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • Gene Products, tax
  • I kappa B beta protein
  • I-kappa B Proteins
  • Interleukin-2
  • Macromolecular Substances
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Receptors, Interleukin-2
  • NF-KappaB Inhibitor alpha