NF-AT-Driven interleukin-4 transcription potentiated by NIP45.
The induction of cytokine gene transcription is mediated in part by the nuclear factor of activated T cells (NF-AT). Factors involved in the mechanisms of NF-AT-mediated transcription are not well understood. A nuclear factor that interacted with the Rel homology domain (RHD) of NF-ATp was identified with the use of a two-hybrid interaction trap. Designated NIP45 (NF-AT interacting protein), it has minimal similarity to any known genes. Transcripts encoding this factor were enriched in lymphoid tissues and testes. NIP45 synergized with NF-ATp and the proto-oncogene c-Maf to activate the interleukin-4 (IL-4) cytokine promoter; transient overexpression of NIP45 with NF-ATp and c-maf in B lymphoma cells induced measurable endogenous IL-4 protein production. The identification of NIP45 advances our understanding of gene activation of cytokines, critical mediators of the immune response.
Hodge
M R
MR
Department of Cancer Biology, Harvard School of Public Health and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Chun
H J
HJ
Rengarajan
J
J
Alt
A
A
Lieberson
R
R
Glimcher
L H
LH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D050778:NFATC Transcription Factors; C494007:Nfatc2 protein, mouse; C102566:Nfatc2ip protein, mouse; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D015847:Interleukin-4