Transcriptional cross-talk: nuclear factors CREM and CREB bind to AP-1 sites and inhibit activation by Jun.
The proteins Fos and Jun dimerize to constitute the transcription factor AP-1 which is known to respond to treatment with phorbol esters. AP-1 binds to 12-O-tetradecanoylphorbol-13-acetate-responsive elements (TREs) palindromic sequences. cAMP-responsive elements (CREs) are very similar to TREs and CRE-binding proteins are similar in structure to Fos and Jun. Thus, the two main signal transduction pathways have closely related nuclear effectors which could possibly overlap and/or cross-talk. The gene CRE modulator (CREM) encodes both antagonists and an activator of the cAMP transcriptional response by alternative splicing. In this report we show that CREM antagonists are able to block the transcriptional activation elicited by c-Jun. The mechanism by which this repression is obtained does not require heterodimerization between CREM and the Fos and/or Jun proteins. In contrast, we show that both CREM and CRE-binding proteins (CREB) are able to bind TREs and therefore compete with c-Jun for this site. Removal of the phosphorylation domain in CREM does not affect the down-regulatory function. We also show that c-Fos does not affect the inhibitory function of CREM on c-Jun and that the transcriptional activation elicited by the other members of the jun family (JunB, JunD, and v-Jun) is also down-regulated by CREM.
Masquilier
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Laboratoire de Génétique Moléculaire des Eucaryotes, U184 de l'Institut National de la Santé et de la Recherche Médicale, Faculté de Médécine, Strasbourg, France.
Sassone-Corsi
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D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator