TGF-beta 1 and cAMP attenuate cyclin A gene transcription via a cAMP responsive element through independent pathways
Résumé
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.
Mots clés
Animals Base Sequence Cell Line Cricetinae Cricetulus Cyclic AMP/*physiology Cyclic AMP Response Element-Binding Protein/*physiology Cyclins/*genetics/metabolism Dna Humans Microinjections Molecular Sequence Data Promoter Regions (Genetics)/physiology Protein Binding *Regulatory Sequences
Genetic Transforming Growth Factor beta/*physiology
Nucleic Acid *Transcription