TGF-BETA-1 AND CAMP ATTENUATE CYCLIN-A GENE-TRANSCRIPTION VIA A CAMP-RESPONSIVE ELEMENT THROUGH INDEPENDENT PATHWAYS

Transforming growth factor beta (TGF-beta) is a potent inhibitor of th e proliferation of many cell lines. The expression of Cyclin A is down -regulated by TGF-beta 1 in Chinese hamster lung fibroblasts and most of this effect is mediated at the transcriptional level through a cAMP -reponsive element (CRE), but does not require a functional cAMP-depen dent protein kinase. However, activation of the cAMP pathway in these cells gives rise to a strong inhibition of proliferation, paralleled b y a down-regulation of Cyclin A promoter activity. This effect require s the integrity of the CRE, suggesting a role for CRE-binding proteins in late G1/S controls.