Pleuron,
Vol. 6, 607-617,
April,
1991, Copyright
0 1991 by Cell Press
Molecular Pathways of Pain: Fodjun-Mediated Activation of a Noncanonical AP-1 Site in the Prodynorphin Gene Jo& R. Naranjo,*+ Britt MellstrGm,*+ Matilde Achaval,* and Paolo Sassone-Corsi+ ’ lnstituto Cajal de Neurociencias Consejo Superior lnvestigaciones Cientificas 28002 Madrid Spain ‘Laboratoire de G&-Gtique Mol&ulaire des Eucaryotes du CNRS IJnitC 184 de GCnie GCnetique et de Biologie MolCculaire de I’INSERM lnstitut de Chimie Biologique f’aculte de MCdecine 67085 Strasbourg Ckdex f:rance
!iummary 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/immune histochemistry, 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-llike sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by i he 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 Fgs/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes. f ntroduction ‘The prodynorphin gene encodes a family of structurally related opioid peptides (Kakidani et al., 1982; Horikawa et al., 1983; Civelli et al:, 1985) that have high affinity for the K subtype of the opiate receptor (Corbett et al., 1982; Schmauss and Yaksh, 1984; Herman and Goldstein, 1985; Millan et al., 1985). The prodynorphin gene iswidelyexpressed in brain and spinal cord
Vol. 6, 607-617,
April,
1991, Copyright
0 1991 by Cell Press
Molecular Pathways of Pain: Fodjun-Mediated Activation of a Noncanonical AP-1 Site in the Prodynorphin Gene Jo& R. Naranjo,*+ Britt MellstrGm,*+ Matilde Achaval,* and Paolo Sassone-Corsi+ ’ lnstituto Cajal de Neurociencias Consejo Superior lnvestigaciones Cientificas 28002 Madrid Spain ‘Laboratoire de G&-Gtique Mol&ulaire des Eucaryotes du CNRS IJnitC 184 de GCnie GCnetique et de Biologie MolCculaire de I’INSERM lnstitut de Chimie Biologique f’aculte de MCdecine 67085 Strasbourg Ckdex f:rance
!iummary 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/immune histochemistry, 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-llike sequences. We demonstrate that only one of these sites is a functional AP-1 element. It is constituted by i he 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 Fgs/Jun trans-activation. Our results suggest that Fos/Jun oncoproteins may function as third messengers in the signal transduction mechanisms of stress/pain processes. f ntroduction ‘The prodynorphin gene encodes a family of structurally related opioid peptides (Kakidani et al., 1982; Horikawa et al., 1983; Civelli et al:, 1985) that have high affinity for the K subtype of the opiate receptor (Corbett et al., 1982; Schmauss and Yaksh, 1984; Herman and Goldstein, 1985; Millan et al., 1985). The prodynorphin gene iswidelyexpressed in brain and spinal cord
