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• W2106032439 abstract "Transcription factor CREB regulates cyclic AMP (cAMP)-dependent gene expression by binding to and activating transcription from cAMP response elements (CREs) in the promoters of target genes. The transcriptional transactivation functions of CREB are activated by its phosphorylation by cAMP-dependent protein kinase A (PKA). In studies of many different phenotypically distinct cells, the CRE of the somatostatin gene promoter is a prototype of a highly cAMP-responsive element regulated by CREB. We now report on a somatostatin-producing rat insulinoma cell line, RIN-1027-B2, in which transcription from the somatostatin gene promoter is paradoxically repressed by CREB. We find that CREB fails to transactivate a CRE-containing somatostatin-chloramphenicol acetyltransferase reporter even when coexpressed with the catalytic subunit of PKA. CAAT box/enhancer-binding protein β (C/EBPβ) and C/EBP-related activating transcription factor bind to the CRE in the promoter of the somatostatin gene and transactivate transcription. CREB binds competitively with C/EBPβ to the somatostatin CRE in vitro and represses C/EBPβ-induced transcription of the CRE-containing somatostatin-chloramphenicol acetyltransferase reporter. The lack of CREB-mediated transcriptional stimulation is due to the presence of a heat-stable inhibitor of PKA that prevents activation of PKA and subsequent CREB phosphorylation in the nucleus. These findings indicate that dephosphorylated CREB is a negative regulator of C/EBP-activated transcription of the somatostatin gene promoter in RIN-1027-B2 cells." @default.
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• W2106032439 date "1995-01-01" @default.
• W2106032439 modified "2023-09-27" @default.
• W2106032439 title "Impaired Cyclic AMP-Dependent Phosphorylation Renders CREB a Repressor of C/EBP-Induced Transcription of the Somatostatin Gene in an Insulinoma Cell Line" @default.
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• W2106032439 doi "https://doi.org/10.1128/mcb.15.1.415" @default.
• W2106032439 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/231983" @default.
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