Transcriptional regulation of CD28 expression by CD28GR, a novel promoter element located in exon 1 of the CD28 gene

The Journal of Immunology : Official Journal of the American Association of Immunologists
C J Lin, R C Tam

Abstract

CD28 provides an essential costimulatory signal required for Ag-mediated T cell activation via the TCR. Although accumulating evidence exists for the signaling properties of CD28, less is known regarding the regulation of CD28 expression. In this study, we have identified a novel promoter element of CD28, CD28GR (GGGGAGGAGGGG), which is located between +181 and +192 in exon 1 of the CD28 gene. Mutations within the 12-bp CD28GR sequence abolished its transcriptional activity. CD28GR contains a Sp1/EGR-1 binding site, which was found to act as the predominant functional element for regulating CD28 gene expression in Jurkat cells. Exon 1/CD28GR-driven transcription in Jurkat cells was augmented by cotransfection with Sp1 or EGR-1 expression plasmid. Similar augmentation was also shown with pharmacologic activation. This study is the first to identify a regulatory element that is critical for conferring constitutive and activation-induced transcriptional activation of the CD28 gene. Furthermore, our results proposed potential involvement of Sp1 in regulating CD28 expression. The linkage between Sp1 and the expression of CD28 has important implications in how viral infections, such as HIV, can induce immunosuppression.

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Citations

Nov 20, 2008·Journal of Experimental & Clinical Cancer Research : CR·Stefania MiccadeiDonato Civitareale
Feb 2, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael CarletonDavid L Wiest
Jul 28, 2009·Human Gene Therapy·Miguel G ToscanoFrancisco Martín
Dec 14, 2007·The Journal of Biological Chemistry·Zhiying HuMiles F Wilkinson
Nov 9, 2019·Journal of Experimental Botany·Sarbottam PiyaTarek Hewezi
Sep 27, 2002·The Journal of Biological Chemistry·Abbe N VallejoJörg J Goronzy
May 6, 2011·Rheumatology International·Aniel Jessica Leticia Brambila-TapiaMario Salazar-Páramo

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