Ca(2+)-dependent prodynorphin transcriptional derepression in neuroblastoma cells is exerted through DREAM protein activity in a kinase-independent manner

Mol Cell Neurosci. 2003 Feb;22(2):135-45. doi: 10.1016/s1044-7431(03)00040-x.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Calcium-Binding Proteins*
  • Central Nervous System / enzymology*
  • Central Nervous System / growth & development
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Enkephalins / biosynthesis*
  • Enkephalins / genetics
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Genes, Regulator / drug effects
  • Genes, Regulator / genetics
  • Humans
  • Kv Channel-Interacting Proteins
  • Mutation / genetics
  • Neuroblastoma
  • Neurons / drug effects
  • Neurons / enzymology*
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / genetics
  • Protein Precursors / biosynthesis*
  • Protein Precursors / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / metabolism
  • Repressor Proteins / drug effects
  • Repressor Proteins / metabolism*
  • Tumor Cells, Cultured

Substances

  • Calcium-Binding Proteins
  • Enkephalins
  • Enzyme Inhibitors
  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • Protein Precursors
  • RNA, Messenger
  • Repressor Proteins
  • Colforsin
  • Caffeine
  • preproenkephalin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium