Redundant expression but selective utilization of nuclear factor of activated T cells family members.
Nuclear factor of activated T cells (NF-AT) complexes regulate the induction of many early T cell activation molecules. Four related proteins can function as the cytoplasmic subunit of NF-AT, and their overlapping expression patterns and the mild phenotype of the NF-ATp null mice suggest that they may be functionally redundant. We characterized the distribution and activation of cytoplasmic NF-AT proteins in mature lymphocytes and found that NF-ATc, NF-ATp, and NF-AT4/x/c3 are co-expressed and co-regulated in mature T and B cells. Each protein forms independent DNA binding complexes, and at physiologic concentrations, NF-ATc and NF-ATp complexes out-compete NF-AT4/x/c3 for occupancy of NF-AT sites from the IL-2, IL-3/granulocyte-macrophage CSF, IL-4, and CD40 ligand genes. This predicts heavily redundant immune regulatory functions of NF-ATp and NF-ATc, but distinct activities for NF-AT4/x/c3. Additionally, Ab interaction with NF-ATp induces high affinity NF-kappaB site interaction, suggesting that nuclear partners may dramatically vary the specificity of the NF-AT family.
Timmerman
L A
LA
The Howard Hughes Medical Institute, Stanford University, CA 94305, USA.
Healy
J I
JI
Ho
S N
SN
Chen
L
L
Goodnow
C C
CC
Crabtree
G R
GR
D000818:Animals; D000906:Antibodies; D001402:B-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*
D000906:Antibodies; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors