https://scholars.lib.ntu.edu.tw/handle/123456789/560424
Title: | Transcriptional regulation of cyclooxygenase-2 in response to proteasome inhibitors involves reactive oxygen species-mediated signaling pathway and recruitment of CCAAT/enhancer-binding protein δ and CREB-binding protein | Authors: | Chen J.-J. Huang W.-C. CHING-CHOW CHEN |
Issue Date: | 2005 | Journal Volume: | 16 | Journal Issue: | 12 | Start page/Pages: | 5579-5591 | Source: | Molecular Biology of the Cell | Abstract: | Inhibition of ubiquitin-proteasome pathway has been shown to be a promising strategy for the treatment of inflammation and cancer. Here, we show that proteasome inhibitors MG132, PSI-1, and lactacystin induce COX-2 expression via enhancing gene transcription rather than preventing protein degradation in the human alveolar NCI-H292 and A549, and gastric AGS epithelial cells. NF-IL6 and CRE, but not NF-κB elements on the COX-2 promoter were involved in the gene transcription event. The binding of CCAAT/enhancer binding protein (C/EBP)β and C/EBPδ to the CRE and NF-IL6 elements, as well as the recruitment of CBP and the enhancement of histone H3 and H4 acetylation on the COX-2 promoter was enhanced by MG132. However, it did not affect the total protein levels of C/EBPβ and C/EBPδ. MG132-induced DNA-binding activity of C/EBPδ, but not C/EBPβ was regulated by p38, PI3K, Src, and protein kinase C. Small interfering RNA of C/EBPδ suppressed COX-2 expression, further strengthening the role of C/EBPδ in COX-2 gene transcription. In addition, the generation of intracellular reactive oxygen species (ROS) in response to MG132 contributed to the activation of MAPKs and Akt. These findings reveal that the induction of COX-2 transcription induced by proteasome inhibitors requires ROS-dependent protein kinases activation and the subsequent recruitments of C/EBPδ and CBP. ? 2005 by The American Society for Cell Biology. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560424 | ISSN: | 10591524 | DOI: | 10.1091/mbc.E05-08-0778 | SDG/Keyword: | benzyloxycarbonylleucylleucylleucinal; CCAAT enhancer binding protein; CCAAT enhancer binding protein beta; CCAAT enhancer binding protein delta; cre recombinase; cyclic AMP responsive element binding protein binding protein; cyclooxygenase 2; DNA; histone H3; histone H4; lactacystin; mitogen activated protein kinase; proteasome inhibitor; protein kinase; protein kinase B; reactive oxygen metabolite; acetylation; article; cell strain A549; cell strain NCI H292; controlled study; DNA binding; enzyme activation; enzyme inhibition; epithelium cell; gene control; gene function; genetic transcription; human; human cell; inflammation; lung alveolus cell; priority journal; promoter region; protein binding; protein degradation; protein expression; protein function; protein modification; protein protein interaction; stomach epithelium; transcription regulation; CCAAT-Enhancer-Binding Protein-delta; Cell Line; CREB-Binding Protein; Cyclooxygenase 2; Gene Expression Regulation, Enzymologic; Humans; Membrane Proteins; Reactive Oxygen Species; RNA, Small Interfering; Signal Transduction; Transcription, Genetic |
Appears in Collections: | 藥理學科所 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.