NF-AT components define a family of transcription factors targeted in T-cell activation

Nature. 1994 Jun 9;369(6480):497-502. doi: 10.1038/369497a0.

Abstract

The NF-AT transcription complex is required for the expression of a group of proteins that collectively coordinate the immune response. Here we purify two proteins encoded by separate genes that represent the pre-existing (p) and cytosolic (c) components of NF-AT. Expression of the full-length complementary DNA encoding NF-ATc activates the interleukin (IL-2) promoter in non-T lymphocytes, whereas a dominant negative of NF-ATc specifically blocks activation of the IL-2 promoter in T lymphocytes, indicating that NF-ATc is required for IL-2 gene expression. NF-ATc RNA expression is largely restricted to lymphoid tissues and is induced upon T-cell activation. The other protein, NF-ATp, is highly homologous to NF-ATc over a limited domain which shows similarity to the Dorsal/Rel family, but has a wider tissue distribution. Agents that increase intracellular Ca2+ or activate protein kinase C independently modify NF-ATc, indicating that distinct signalling pathways converge on NF-ATc to regulate its function.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium / metabolism
  • Cattle
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytosol / metabolism
  • DNA, Complementary
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Interleukin-2 / genetics
  • Lymphocyte Activation* / genetics
  • Mice
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Protein Kinase C / metabolism
  • Protein Processing, Post-Translational
  • RNA, Messenger / biosynthesis
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • NFATC1 protein, human
  • NFATC2 protein, human
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Protein Kinase C
  • Calcium

Associated data

  • GENBANK/U08015