Molecular pathways of pain: Fos/Jun-mediated activation of a noncanonical AP-1 site in the prodynorphin gene.
Noxious stimulation provokes the activation of genes that are thought to play a crucial role in the phenomena of stress and pain. Among these is the prodynorphin gene. By double-labeling in situ hybridization/immunohistochemistry, we show that increased prodynorphin gene expression is preceded, in the same neurons, by an early induction of c-fos. Inspection of the prodynorphin promoter region revealed the presence of several AP-1-like sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by the noncanonical TGACAAACA sequence, in which the palindromic structure is partly conserved by the 3' terminal CA dinucleotide. Transfection experiments in NCB20 neuroblastoma cells indicated that this site is a target of Fos/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes.
Naranjo
J R
JR
Instituto Cajal de Neurociencias, Consejo Superior Investigaciones Cientificas, Madrid, Spain.
Mellström
B
B
Achaval
M
M
Sassone-Corsi
P
P
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D004745:Enkephalins / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D051381:Rats / Q000235:genetics; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D004745:Enkephalins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; C033660:preproenkephalin; D013755:Tetradecanoylphorbol Acetate