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 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.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D004247:DNA; D006801:Humans; D008845:Microinjections; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology*
D017362:Cyclic AMP Response Element-Binding Protein; D016213:Cyclins; D016212:Transforming Growth Factor beta; D004247:DNA; D000242:Cyclic AMP