TY - JOUR
T1 - c-Rel regulation of IL-2 gene expression may be mediated through activation of AP-1
AU - Shapiro, Virginia Smith
AU - Mollenauer, Marianne Newton
AU - Greene, Warner C.
AU - Weiss, Arthur
PY - 1996/11/1
Y1 - 1996/11/1
N2 - T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-κB family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-κB site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In jurkat TAg cells, overexpression of c-Rel increased AP-1 activation ~17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.
AB - T cell activation by antigen/MHC induces the expression of several genes critical to the immune response, including interleukin-2. T cells from mice deficient for the NF-κB family member c-rel cannot activate IL-2 gene expression. However, mutating the NF-κB site in the IL-2 promoter has only moderate effects. To investigate additional ways c-Rel could regulate IL-2 gene expression, we determined whether c-rel overexpression could increase the activity of other transcription factors involved in IL-2 promoter regulation: NF-AT, Oct/OAP (ARRE-1), and AP-1. In jurkat TAg cells, overexpression of c-Rel increased AP-1 activation ~17-fold. Moreover, AP-1 activity stimulated by anti-TCR Abs or PMA/ionomycin was further increased by c-Rel overexpression. c-Rel overexpression did not affect NF-AT or ARRE-1 activity. Additionally, overexpression of c-Rel activated the nonconsensus AP-1 site from the IL-2 promoter (NF-IL-2B), although to a lesser extent, approximately sixfold. AP-1 activation required both the DNA binding and transactivation domains of c-Rel. Our results may provide an explanation for the effect on IL-2 gene activation in c-rel-deficient mice.
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U2 - 10.1084/jem.184.5.1663
DO - 10.1084/jem.184.5.1663
M3 - Article
C2 - 8920856
AN - SCOPUS:0029826970
SN - 0022-1007
VL - 184
SP - 1663
EP - 1669
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 5
ER -