Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat Schwannoma cell line D6P2T constitutively expresses the mRNA encoding the major myelin protein, P0, but only expresses the mRNA encoding myelin basic protein (MBP) after exposure to forskolin or other substances that raise the levels of intracellular cyclic AMP. In this study we have investigated the molecular basis for forskolin induction of MBP transcription in D6P2T cells. We have found that a 9-bp sequence element, CACTTGATC, located between nucleotides -85 and -77 in the MBP promoter, is necessary for forskolin induction of chloramphenicol acetyltransferase (CAT) expression after transient transfection of MBP promoter-CAT fusion constructs into D6P2T cells. Although similar DNase I footprints, one of which is located within the above 9-bp sequence element, are produced by nuclear extracts prepared from both forskolin-treated and untreated cells, this same sequence can be shown to interact with a forskolin-inducible protein complex using an electrophoretic mobility shift assay. In addition, mutation of this 9-bp sequence abolishes both formation of this new protein--DNA complex and forskolin-inducible CAT expression from the heterologous SV40 promoter. Finally, we have shown that the appearance of this forskolin-inducible protein--DNA complex precedes that of MBP mRNA. Taken together, these data strongly support the notion that the induction of MBP transcription by forskolin in D6P2T cells is mediated by the binding of a forskolin-inducible protein complex to the MBP promoter sequence CACTTGATC.
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PMID:A novel cyclic AMP response element, CACTTGATC, mediates forskolin induction of the myelin basic protein promoter in the rat Schwannoma line, D6P2T. 751 47

Using stable cell lines containing a series of deletions of the myelin basic protein (MBP) promoter directing the bacterial chloramphenicol acetyltransferase gene in a peripheral neurinoma cell line, we have studied the sequences in the MBP promoter needed for induction by cyclic AMP. Stimulation of expression from the MBP promoter by cyclic AMP is not a rapid response. Expression begins after 24 h and reaches a maximum at approximately 72 h. The results from the stable transformants indicate at least one region that appears to be essential to the induction of transcription directed by the MBP promoter. The region that is necessary for induction does not contain a consensus cyclic AMP response element. A specific binding site involved in the induction by cyclic AMP was localized to an NFI binding site.
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PMID:Binding at an NFI site is modulated by cyclic AMP-dependent activation of myelin basic protein gene expression. 768 65