Cyclic adenosine 5′-monophosphate response element modulator is responsible for the decreased expression of c-fos and activator protein-1 binding in T cells from …

VC Kyttaris, YT Juang, K Tenbrock… - The Journal of …, 2004 - journals.aai.org
The Journal of Immunology, 2004journals.aai.org
T cells from patients with systemic lupus erythematosus express increased levels of the
cAMP response element modulator (CREM) that has been shown to bind to the IL-2
promoter and suppress its activity. In this study, we demonstrate that CREM binds to the
proximal promoter of the c-fos proto-oncogene in live systemic lupus erythematosus T cells
and represses its expression following stimulation in vitro. Decreased levels of c-fos protein
result in decreased AP-1 activity, as determined in shift assays. Blockade of the translation of …
Abstract
T cells from patients with systemic lupus erythematosus express increased levels of the cAMP response element modulator (CREM) that has been shown to bind to the IL-2 promoter and suppress its activity. In this study, we demonstrate that CREM binds to the proximal promoter of the c-fos proto-oncogene in live systemic lupus erythematosus T cells and represses its expression following stimulation in vitro. Decreased levels of c-fos protein result in decreased AP-1 activity, as determined in shift assays. Blockade of the translation of CREM mRNA with an antisense CREM vector increases the expression of c-fos and the AP-1 activity. The levels of c-fos mRNA vary with disease activity. We conclude that CREM represses the expression of c-fos and limits the activity of the enhancer AP-1. Thus, CREM is involved indirectly in the modulation of transcriptional regulation of multiple genes including IL-2.
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