Nuclear appearance of a factor that binds the CD28 response element within the interleukin-2 enhancer correlates with interleukin-2 production.
Activation of T lymphocytes requires the combined signaling of the T cell receptor and costimulatory molecules such as CD28. The ability of T cells to produce interleukin-2 (IL-2) is a critical control point in T lymphocyte activation. The IL-2 enhancer contains a functional motif named CD28 response element (CD28RE) that serves a role as a target for mitogenic T cell activation signals. The CD28RE sequence reveals similarity to the consensus kappaB binding motif. Here we demonstrate that CD28RE binds an inducible protein with a molecular mass of approximately 35 kDa called nuclear factor of mitogenic-activated T cells (NF-MATp35) that is clearly different from the known NF- kappaB/Rel family members. Induction of NF-MATp35 was shown to depend on de novo protein synthesis and was restricted to T cells that received a mitogenic combination of T cell stimuli, not necessarily including CD28 signaling. Nonmitogenic T cell stimulation did not result in appearance of NF-MATp35. These results indicate that mitogenic combinations of T cell activation signals are integrated at the level of NF-MATp35 induction. Similar to its effect on IL-2 production, cyclosporin A inhibited the induction of NF-MATp35. Taken together, these data demonstrate that the nuclear appearance of NF-MATp35 shows excellent correlation with IL-2 production, which is a unique characteristic among nuclear factors implicated in the control of IL-2 gene expression.
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Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Department of Autoimmune Diseases, Amsterdam, 1066 CX The Netherlands.
Bakker
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Rensink
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Doerre
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Aarden
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Verweij
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D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism*; D016384:Consensus Sequence; D003432:Cross-Linking Reagents; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D003432:Cross-Linking Reagents; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D009687:Nuclear Proteins; D014157:Transcription Factors; D016572:Cyclosporine; D003513:Cycloheximide