Abstract
Prodynorphin transcription has been postulated as an important molecular mechanism involved in adaptation/repair processes. Expression of prodynorphin is modulated according to the levels of the second messengers cAMP and Ca(2+). In the neuroblastoma cell lines, the increase of prodynorphin mRNA levels is coupled to an elevation of intracellular cAMP levels. Promoter analyses have revealed that the DRE site, a silencer element present in the prodynorphin promoter, is involved in PKA-dependent prodynorphin derepression. In this way, DREAM, a calcium-dependent repressor, plays an outstanding role. In this study, Ca(2+) release from internal stores has been found to promote an increase of prodynorphin mRNA levels in NB69 cells. Surprisingly, Ca(2+)-dependent prodynorphin gene transcription was insensitive to the broad-spectrum kinase inhibitors and sensitive to agents that alter internal Ca(2+) accumulation. Moreover, we demonstrate that in NB69 cells, the Ca(2+) signaling pathway uses DREAM as an effector to evoke prodynorphin transcription derepression in a kinase-independent manner.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caffeine / pharmacology
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Calcium / metabolism
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Calcium / pharmacology
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Calcium-Binding Proteins*
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Central Nervous System / enzymology*
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Central Nervous System / growth & development
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Colforsin / pharmacology
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Cyclic AMP / metabolism
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Cyclic AMP-Dependent Protein Kinases / drug effects
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Enkephalins / biosynthesis*
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Enkephalins / genetics
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics*
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Genes, Regulator / drug effects
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Genes, Regulator / genetics
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Humans
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Kv Channel-Interacting Proteins
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Mutation / genetics
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Neuroblastoma
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Neurons / drug effects
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Neurons / enzymology*
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Protein Biosynthesis / drug effects
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Protein Biosynthesis / genetics
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Protein Precursors / biosynthesis*
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Protein Precursors / genetics
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Repressor Proteins / drug effects
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Repressor Proteins / metabolism*
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Tumor Cells, Cultured
Substances
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Calcium-Binding Proteins
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Enkephalins
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Enzyme Inhibitors
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KCNIP3 protein, human
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Kv Channel-Interacting Proteins
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Protein Precursors
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RNA, Messenger
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Repressor Proteins
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Colforsin
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Caffeine
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preproenkephalin
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Calcium