High mobility group protein I(Y) is required for function and for c-Rel binding to CD28 response elements within the GM-CSF and IL-2 promoters.
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.
Himes
S R
SR
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, South Australia.
Coles
L S
LS
Reeves
R
R
Shannon
M F
MF
D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D019169:Jurkat Cells; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors / Q000378:metabolism
D018106:CD28 Antigens; D006609:High Mobility Group Proteins; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors; D025741:HMGA1a Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor