Transforming growth factor beta (TGF-beta) is a potent inhibitor of the 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-responsive element (CRE), but does not require a functional cAMP-dependent protein kinase. However, activation of the cAMP pathway in these cells gives rise to a strong inhibition of proliferation, paralleled by a down-regulation of Cyclin A promoter activity. This effect requires the integrity of the CRE, suggesting a role for CRE-binding proteins in late G1/S controls.
TGF-beta 1 and cAMP attenuate cyclin A gene transcription via a cAMP responsive element through independent pathways
Barlat, I.; Henglein, B.; Plet, A.; Lamb, N.; Fernandez, A.; McKenzie, F.; Pouyssegur, J.; Vie, A.; Blanchard, J. M.
1995-10-05 / vol 11 / pages 1309-18
Humans; Animals; *Transcription, Genetic; Molecular Sequence Data; Protein Binding; Base Sequence; Cell Line; Cricetinae; *Regulatory Sequences, Nucleic Acid; Transforming Growth Factor beta/*physiology; Dna; Cyclins/*genetics/metabolism; Microinjections; Cricetulus; Promoter Regions (Genetics)/physiology; Cyclic AMP Response Element-Binding Protein/*physiology; Cyclic AMP/*physiology