Ca2+-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 Ca2+. 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, Ca2+ release from internal stores has been found to promote an increase of prodynorphin mRNA levels in NB69 cells. Surprisingly, Ca2+-dependent prodynorphin gene transcription was insensitive to the broad-spectrum kinase inhibitors and sensitive to agents that alter internal Ca2+ accumulation. Moreover, we demonstrate that in NB69 cells, the Ca2+ signaling pathway uses DREAM as an effector to evoke prodynorphin transcription derepression in a kinase-independent manner. (C) 2003 Elsevier Science (USA). All rights reserved.