The role of NF-AT transcription factors in T cell activation and differentiation

Biochim Biophys Acta. 2000 Oct 20;1498(1):1-18. doi: 10.1016/s0167-4889(00)00082-3.


The family of genuine NF-AT transcription factors consists of four members (NF-AT1 [or NF-ATp], NF-AT2 [or NF-ATc], NF-AT3 and NF-AT4 [or NF-ATx]) which are characterized by a highly conserved DNA binding domain (is designated as Rel similarity domain) and a calcineurin binding domain. The binding of the Ca(2+)-dependent phosphatase calcineurin to this region controls the nuclear import and exit of NF-ATs. This review deals (1) with the structure of NF-AT proteins, (2) the DNA binding of NF-AT factors and their interaction with AP-1, (3) NF-AT target genes, (4) signalling pathways leading to NF-AT activation: the role of protein kinases and calcineurin, (5) the nuclear entry and exit of NF-AT factors, (6) transcriptional transactivation by NF-AT factors, (7) the structure and expression of the chromosomal NF-AT2 gene, and (8) NF-AT factors in Th cell differentiation. The experimental data presented and discussed in the review show that NF-AT factors are major players in the control of T cell activation and differentiation and, in all likelihood, also of the cell cycle and apoptosis of T lymphocytes.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Calcineurin / metabolism
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Humans
  • Lymphocyte Activation
  • Mutation
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Protein Conformation
  • Signal Transduction
  • T-Lymphocytes / physiology*
  • Th1 Cells / physiology
  • Th2 Cells / physiology
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factor AP-1
  • Transcription Factors
  • DNA
  • Calcineurin