Ca(2+)-dependent prodynorphin transcriptional derepression in neuroblastoma cells is exerted through DREAM protein activity in a kinase-independent manner.
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.
Campos
David
D
Centro Nacional de Biotecnologia (CNB), Universidad Autónoma de Madrid, Cantoblanco, E-28049, Madrid, Spain
Jiménez-Díaz
Lydia
L
Carrión
Angel M
AM
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins; D002490:Central Nervous System / Q000201:enzymology* / Q000254:growth & development; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005809:Genes, Regulator / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051605:Kv Channel-Interacting Proteins; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D012097:Repressor Proteins / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D004745:Enkephalins; D004791:Enzyme Inhibitors; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D012097:Repressor Proteins; D005576:Colforsin; D002110:Caffeine; C033660:preproenkephalin; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium