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. 1991 Jun 15;88(12):5448–5452. doi: 10.1073/pnas.88.12.5448

Transcriptional antagonist cAMP-responsive element modulator (CREM) down-regulates c-fos cAMP-induced expression.

N S Foulkes 1, B M Laoide 1, F Schlotter 1, P Sassone-Corsi 1
PMCID: PMC51890  PMID: 1647033

Abstract

Protooncogene c-fos is induced by activation of adenylate cyclase through the major cAMP-responsive element (CRE) centered at position -60 of the promoter. cAMP induction is followed by a rapid decrease in transcriptional rate, reminiscent of down-regulation after serum stimulation. Fos protein is known to negatively autoregulate serum-induced transcription of c-fos promoter, but whether Fos is responsible for down-regulation of cAMP-induced transcription is unclear. Here we show that Fos is unable to down-regulate CRE-mediated activation. We present evidence that the transcriptional antagonist CRE modulator (CREM) can bind to c-fos CRE and heterodimerize with activator CRE-binding protein, thereby blocking cAMP induction. Furthermore, expression of antisense CREM enhances c-fos basal and cAMP-induced transcription. CREM does not antagonize serum-induced transcription; therefore, we conclude that down-regulation of c-fos is exerted by different effectors, depending upon which signal transduction pathway is activated. We speculate that, by its c-fos down-regulatory function, CREM may act as an antioncogene.

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