GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes.
Interleukin 16 (IL-16) is a chemotactic cytokine that binds to the CD4 receptor and affects the activation of T cells and replication of HIV. It is expressed as a large 67-kDa precursor protein (pro-IL-16) in lymphocytes, macrophages, and mast cells, as well as in airway epithelial cells from asthmatics after ... challenge with allergen. This pro-IL-16 is subsequently processed to the mature cytokine of 13 kDa. To study the expression of IL-16 at the transcriptional level, we cloned the human chromosomal IL-16 gene and analyzed its promoter. The human IL-16 gene consists of seven exons and six introns. The 5' sequences up to nucleotide -120 of the human and murine IL-16 genes share >84% sequence homology and harbor promoter elements for constitutive and inducible transcription in T cells. Although both promoters lack any TATA box, they contain two CAAT box-like motifs and three binding sites of GA-binding protein (GABP) transcription factors. Two of these motifs are part of a highly conserved and inducible dyad symmetry element shown previously to control a remote IL-2 enhancer and the CD18 promoter. In concert with the coactivator CREB binding protein/p300, which interacts with GABPalpha, the binding of GABPalpha and -beta to the dyad symmetry element controls the induction of IL-16 promoter in T cells. Supplementing the data on the processing of pro-IL-16, our results indicate the complexity of IL-16 expression, which is tightly controlled at the transcriptional and posttranslational levels in T lymphocytes.
Mesh Terms:
Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, E1A-Associated p300 Protein, GA-Binding Protein Transcription Factor, Gene Expression Regulation, Humans, Interleukin-16, Mice, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Protein Precursors, Recombinant Proteins, Sequence Alignment, Sequence Homology, Nucleic Acid, T-Lymphocytes, Trans-Activators, Transcription Factors
Animals, Base Sequence, Chromosome Mapping, Cloning, Molecular, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, E1A-Associated p300 Protein, GA-Binding Protein Transcription Factor, Gene Expression Regulation, Humans, Interleukin-16, Mice, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Protein Precursors, Recombinant Proteins, Sequence Alignment, Sequence Homology, Nucleic Acid, T-Lymphocytes, Trans-Activators, Transcription Factors
Proc Natl Acad Sci U S A
Date: Feb. 16, 1999
PubMed ID: 09990060
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