Role of CBP/p300 and SRC-1 in Transcriptional Regulation of the Pulmonary Surfactant Protein-A (SP-A) Gene by Thyroid Transcription Factor-1 (TTF-1) *
作者： Ming Yi , Guo-Xia Tong , Barbara Murry , Carole R. Mendelson
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摘要: Surfactant protein-A(SP-A) gene expression is developmentally regulated in fetal lung type II cells and enhanced by cAMP. cAMP stimulation ofSP-A mediated protein kinase A (PKA) phosphorylation of thyroid transcription factor 1 (TTF-1), expressed selectively developing epithelium. In this study, we analyzed roles CREB-binding (CBP) steroid receptor coactivator-1 (SRC-1) TTF-1 regulation SP-A expression. Upon differentiation human culture, nuclear localization CBP, SRC-1, increased ductular epithelium association with cell induction transient transfections, CBP SRC-1 acted synergistically to increase promoter activity. Overexpression PKA catalytic subunit hSP-A activation plus TTF-1. Adenoviral E1A overexpression reduced ± activity, suggesting a role endogenous CBP/p300. interacted CBPin vitro. immunodepletion from extracts binding the element upstream gene. cultured cells, acetylation. This suggests that cAMP-mediated facilitates interaction resulting its hyperacetylation, further enhancing DNA-binding transcriptional
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