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-induced
NF-
B1 Transcription
By
From the * Lineberger Comprehensive Cancer Center, and NF- Department of Biology, University of
North Carolina, Chapel Hill, North Carolina 27599-7295
B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-B. Previously, we and others have demonstrated that NF-B regulates the
NF-B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell
lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-B1 encoding transcripts than cells stimulated with tumor
necrosis factor-
, despite the fact that both stimuli activate NF-B. Characterization of the NF-B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/
PHA-mediated induction as well as the synergistic activation observed after the expression of
the RelA subunit of NF-B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense
Egr-1 RNA were inhibited in their ability to upregulate NF-B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-B may have
important ramifications in T cell development by upregulating NF-B1 gene expression.
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