Abstract
CD28 response elements (CD28REs) within cytokine promoters are variant NF-kappaB-binding sites and are essential for transcription in response to CD28 receptor activation in T cells. We show that the CK-1 element (CD28RE) within the GM-CSF promoter binds the RelA and c-Rel transcription factors in response to CD28 activation. We further show that the high mobility group protein HMG I(Y) can bind to the CD28REs of both GM-CSF and IL-2 and that this binding is critical for c-Rel, but not RelA, binding. A second NF-kappaB site in the GM-CSF promoter that binds p50 and RelA, but neither c-Rel nor HMG I(Y), failed to respond to CD28 activation. Expression of HMG I or c-Rel antisense RNA inhibited CD28 activation of the IL-2 and GM-CSF promoters, implying that HMG I(Y) enhancement of c-Rel binding plays an important role in the activity of the CD28REs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD28 Antigens / genetics
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CD28 Antigens / metabolism*
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Enhancer Elements, Genetic / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
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HMGA1a Protein
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High Mobility Group Proteins / physiology*
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Humans
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Interleukin-2 / biosynthesis
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Interleukin-2 / genetics*
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Jurkat Cells
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Promoter Regions, Genetic / immunology*
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Protein Binding / genetics
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Protein Binding / immunology
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-rel
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Transcription Factors / metabolism
Substances
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CD28 Antigens
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High Mobility Group Proteins
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Interleukin-2
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-rel
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Transcription Factors
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HMGA1a Protein
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Granulocyte-Macrophage Colony-Stimulating Factor