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p300/Cyclic AMP-responsive element binding-binding protein mediates transcriptional coactivation by the CD28 T cell

Sarada L Nandiwada1, Wei Li, Ruan Zhang

  • 1Rheumatic and Autoimmune Diseases Division, and Center for Immunology, University of Minnesota Medical School, 312 Church Street SE, Minneapolis, MN 55455, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 21, 2006
PubMed

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.

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