Functional role of NF-IL6beta and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase 2 gene.
NF-IL6beta regulates gene expression and plays function roles in many tissues. The EGF-regulated cyclooxygenase-2 (cox-2) expression is mediated through p38(MAPK) signaling pathway and positively correlates with NF-IL6beta expression in A431 cells. NF-IL6beta coordinated with c-Jun on cox-2 transcriptional activation by reporter and small interfering RNA assays. NF-IL6beta could directly bind ... to CCAAT/enhancer-binding protein (C/EBP) and cyclic AMP-response element (CRE) sites of the cox-2 promoter by in vitro-DNA binding assay. The C/EBP site was important for basal and, to a lesser extent, for EGF-regulated cox-2 transcription, while the CRE site was a more specific response to EGF inducibility of cox-2 gene. SUMO1 expression attenuated EGF- and NF-IL6beta-induced cox-2 promoter activities. NF-IL6beta was found to be sumoylated by in vivo- and in vitro-sumoylation assays, and the SUMO1-NF-IL6beta (suNF-IL6beta) lost its ability to interact with p300 in in vitro-binding assay. NF-IL6beta was also acetylated by p300, and acetylation of NF-IL6beta enhanced the cox-2 promoter activity stimulated by NF-IL6beta itself. In vivo-DNA binding assay demonstrated that EGF stimulated the recruitment of p300 and NF-IL6beta to the cox-2 promoter, yet promoted the dissociation of SUMO1-modificated proteins from the promoter. These results indicated that NF-IL6beta plays a pivotal role in the regulation of basal and EGF-induced cox-2 transcription.
Mesh Terms:
Acetylation, Animals, Binding Sites, CCAAT-Enhancer-Binding Protein-delta, CCAAT-Enhancer-Binding Proteins, Cell Cycle Proteins, Cell Line, Tumor, Cyclic AMP, Cyclooxygenase 2, Epidermal Growth Factor, Gene Expression Regulation, Enzymologic, Histone Acetyltransferases, Imidazoles, Promoter Regions, Genetic, Protein Kinase Inhibitors, Protein Processing, Post-Translational, Pyridines, Response Elements, SUMO-1 Protein, Transcription Factors, Transcriptional Activation, p300-CBP Transcription Factors, p38 Mitogen-Activated Protein Kinases
Acetylation, Animals, Binding Sites, CCAAT-Enhancer-Binding Protein-delta, CCAAT-Enhancer-Binding Proteins, Cell Cycle Proteins, Cell Line, Tumor, Cyclic AMP, Cyclooxygenase 2, Epidermal Growth Factor, Gene Expression Regulation, Enzymologic, Histone Acetyltransferases, Imidazoles, Promoter Regions, Genetic, Protein Kinase Inhibitors, Protein Processing, Post-Translational, Pyridines, Response Elements, SUMO-1 Protein, Transcription Factors, Transcriptional Activation, p300-CBP Transcription Factors, p38 Mitogen-Activated Protein Kinases
Nucleic Acids Res.
Date: Jan. 07, 2006
PubMed ID: 16397300
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