p300/Cyclic AMP-responsive element binding-binding protein mediates transcriptional coactivation by the CD28 T cell costimulatory receptor.
During Ag stimulation of T cells, the recognition of B7 molecules by the CD28 costimulatory receptor increases the level of c-Fos, a component of the AP-1 transactivator known to bind the 5' Il2 gene enhancer. In this study, we show that the costimulation of Fos transcription by CD28 is associated with increased binding of p300/CREB-binding protein (CBP) molecules at the Fos promoter, and is blocked by an adenoviral E1A molecular antagonist of p300/CBP. Furthermore, transcriptional activation by a C-terminal domain of CBP is strengthened when CD28 molecules are actively signaling. This increased amount and activity of p300/CBP molecules at the Fos gene correlated with higher histone H4 acetylation and RNA polymerase II association with the promoter. These data suggest a global mechanism whereby CD28 signaling influences the rate and intensity of new gene expression during Ag recognition via direct control over the coactivator function of p300/CBP.
Nandiwada
Sarada L
SL
Rheumatic and Autoimmune Diseases Division, and Center for Immunology, University of Minnesota Medical School, 312 Church Street SE, Minneapolis, MN 55455, USA.
Li
Wei
W
Zhang
Ruan
R
Mueller
Daniel L
DL
D000107:Acetylation; D000818:Animals; D018106:CD28 Antigens / Q000378:metabolism* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D006657:Histones / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012319:RNA Polymerase II / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D015533:Transcriptional Activation / Q000276:immunology*; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism; D050880:p300-CBP Transcription Factors / Q000378:metabolism / Q000502:physiology*
D018106:CD28 Antigens; C494113:Elk1 protein, mouse; D006657:Histones; D016760:Proto-Oncogene Proteins c-fos; D050807:ets-Domain Protein Elk-1; D012694:Serine; D050882:CREB-Binding Protein; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II