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 patients with systemic lupus erythematosus.
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.
Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vasileios C
VC
Kyttaris
Yuang-Taung
YT
Juang
Klaus
K
Tenbrock
Arthur
A
Weinstein
George C
GC
Tsokos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000242:Cyclic AMP / Q000378:metabolism*; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D020218:Response Elements; D013601:T-Lymphocytes / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP