Transcription factor regulation of prodynorphin gene expression following rat hindpaw inflammation.

Abstract	Both c-Fos and prodynorphin mRNA and peptide increase unilaterally in nociceptive-specific neurons in the lumbar rat spinal cord during chronic hindpaw inflammation. To study the mechanisms underlying prodynorphin gene expression, we examined transcription factors and their interactions at the CRE/AP-1-like site, DYNCRE3, found in the prodynorphin gene promoter. CREB repressed while c-Fos and c-Jun activated transcription through the DYNCRE3 site in transient co-transfections in PC12 cells. Following inflammation of the rat hindpaw, immunostaining demonstrated a bilateral increase in phosphorylated CREB (P-CREB)-positive neurons in the spinal cord. Gel supershift studies showed that spinal cord extracts contained CREB, P-CREB, and phosphorylated c-Jun (P-c-Jun) proteins that bound to the DYNCRE3 site. We propose a model in which inflammation-induced phosphorylation of CREB relieves CREB repression at the DYNCRE3 site, P-CREB binds to the c-Fos promoter, and Fos/Fra, P-CREB, and P-c-Jun interact at the DYNCRE3 site to activate prodynorphin gene transcription.
Authors	D J Messersmith, D J Kim, M J Iadarola
Journal	Brain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 53 Issue 1-2 Pg. 260-9 (Jan 1998) ISSN: 0169-328X [Print] Netherlands
PMID	9473689 (Publication Type: Journal Article)
Chemical References	Cyclic AMP Response Element-Binding Protein Enkephalins Protein Precursors Proto-Oncogene Proteins c-fos Proto-Oncogene Proteins c-jun Recombinant Proteins Transcription Factor AP-1 Transcription Factors preproenkephalin
Topics	Animals Binding Sites Cell Nucleus (metabolism) Cyclic AMP Response Element-Binding Protein (biosynthesis, metabolism) Enkephalins (biosynthesis) Gene Expression Regulation Hindlimb Inflammation (metabolism) Male Models, Neurological Neurons (metabolism, physiology) PC12 Cells Phosphorylation Promoter Regions, Genetic Protein Precursors (biosynthesis) Proto-Oncogene Proteins c-fos (metabolism) Proto-Oncogene Proteins c-jun (metabolism) Rats Rats, Sprague-Dawley Recombinant Proteins (biosynthesis) Spinal Cord (metabolism, physiopathology) Transcription Factor AP-1 (metabolism) Transcription Factors (metabolism) Transcription, Genetic Transfection

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