Critical role of C/EBPdelta and C/EBPbeta factors in the stimulation of the cyclooxygenase-2 gene transcription by interleukin-1beta in articular chondrocytes.

Publisher: Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies Country of Publication: England NLM ID: 0107600 Publication Model: Print Cited Medium: Print ISSN: 0014-2956 (Print) Linking ISSN: 00142956 NLM ISO Abbreviation: Eur J Biochem Subsets: MEDLINE

Publication: -2004: Oxford, UK : Blackwell Science Ltd. on behalf of the Federation of European Biochemical Societies
Original Publication: Berlin, New York, Springer.

Transcription Factors* ; Transcription, Genetic*; CCAAT-Enhancer-Binding Protein-beta/*physiology ; CCAAT-Enhancer-Binding Proteins/*physiology ; Cartilage, Articular/*metabolism ; Chondrocytes/*metabolism ; Interleukin-1/*metabolism ; Isoenzymes/*genetics ; Prostaglandin-Endoperoxide Synthases/*genetics; Animals ; Base Sequence ; Binding Sites ; CCAAT-Enhancer-Binding Protein-delta ; Cell Nucleus/metabolism ; Cells, Cultured ; Chloramphenicol O-Acetyltransferase/metabolism ; Cyclooxygenase 2 ; Female ; Gene Deletion ; Gene Expression Regulation ; Humans ; Kinetics ; Membrane Proteins ; Models, Biological ; Molecular Sequence Data ; Mutagenesis ; Plasmids/metabolism ; Promoter Regions, Genetic ; Protein Binding ; Proto-Oncogene Proteins c-rel/metabolism ; Rabbits ; Sequence Homology, Nucleic Acid

The activity of the [-831; +103] promoter of the human cyclooxygenase-2 gene in cultured rabbit chondrocytes is stimulated 2.9 +/- 0.3-fold by interleukin-1beta and this stimulation depends on [-132; -124] C/EBP binding-and [-223; -214] NF-kappaB binding-sites. The C/EBPbeta and C/EBPdelta factors bind to the [-132; -124] sequence. The [-61; -53] sequence is also recognized by C/EBPbeta and C/EBPdelta as well as USF. Mutation of the whole [-61; -53] sequence abolished the stimulation of transcription but single mutations of the C/EBP or USF site did not alter the activity of the promoter, suggesting that the factors bound to the proximal [-61; -53] sequence interact with different members of the general transcription machinery. The [-223; -214] site binds only the p50/p50 homodimer and a non-rel-related protein, but not the transcriptionally active heterodimer p50/p65. The p50/p50 homodimer could interact with the C/EBP family members bound to the [-132; -124] sequence for full stimulation of the COX-2 transcription by interleukin-1beta in chondrocytes. By contrast, the [-448; -449] sequence binds with a low affinity both the p50/p50 homodimeric and p50/p65 heterodimeric forms of NF-kappaB but has no role in the regulation of the human COX-2 promoter in chondrocytes.

0 (CCAAT-Enhancer-Binding Protein-beta)
0 (CCAAT-Enhancer-Binding Proteins)
0 (CEBPD protein, human)
0 (Interleukin-1)
0 (Isoenzymes)
0 (Membrane Proteins)
0 (Proto-Oncogene Proteins c-rel)
0 (Transcription Factors)
142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
EC 1.14.99.1 (Cyclooxygenase 2)
EC 1.14.99.1 (PTGS2 protein, human)
EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)

Date Created: 20001118 Date Completed: 20010201 Latest Revision: 20190620

20240829

10.1046/j.1432-1033.2000.01778.x

11082190