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Mol. Cell. Biol., 06 1995, 3301-3309, Vol 15, No. 6
Copyright © 1995, American Society for Microbiology

Cell cycle regulation of cyclin A gene expression by the cyclic AMP- responsive transcription factors CREB and CREM

C Desdouets, G Matesic, CA Molina, NS Foulkes, P Sassone-Corsi, C Brechot and J Sobczak-Thepot
Institut National de la Sante et de la Recherche Medicale U370, Faculte Necker, Paris, France.

Cyclin A is a pivotal regulatory protein which, in mammalian cells, is involved in the S phase of the cell cycle. Transcription of the human cyclin A gene is cell cycle regulated. We have investigated the role of the cyclic AMP (cAMP)-dependent signalling pathway in this cell cycle- dependent control. In human diploid fibroblasts (Hs 27), induction of cyclin A gene expression at G1/S is stimulated by 8-bromo-cAMP and suppressed by the protein kinase A inhibitor H89, which was found to delay S phase entry. Transfection experiments showed that the cyclin A promoter is inducible by activation of the adenylyl cyclase signalling pathway. Stimulation is mediated predominantly via a cAMP response element (CRE) located at positions -80 to -73 with respect to the transcription initiation site and is able to bind CRE-binding proteins and CRE modulators. Moreover, activation by phosphorylation of the activators CRE-binding proteins and CRE modulator tau and levels of the inducible cAMP early repressor are cell cycle regulated, which is consistent with the pattern of cyclin A inducibility by cAMP during the cell cycle. These results suggest that the CRE is, at least partly, implicated in stimulation of cyclin A transcription at G1/S.


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