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The role of translational regulation in ultraviolet light‐induced cyclooxygenase‐2 expression
Author(s) -
Carpenter Oliver Luke,
László Csaba,
Fayad Sherine,
Wu Shiyong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.511.2
Subject(s) - intracellular , phosphorylation , chemistry , microbiology and biotechnology , translational regulation , ingenuity , translation (biology) , biology , messenger rna , biochemistry , gene , neoclassical economics , economics
Ultraviolet light (UV) induces a prolonged expression of Cyclooxygenase‐2 (COX‐2). While transcriptional regulation of COX‐2 expression is intensively studied, the role of translational regulation of COX‐2 synthesis upon UV‐irradiation is not yet clear. Through the use of Ingenuity Pathway Analysis(tm) software's Canonical Pathway Analysis, we proposed a novel alpha subunit of the eukaryotic initiation factor 2 (eIF2α) phosphorylation‐centered network for the regulation of COX‐2 expression after UV‐irradiation. Our data shows that UV light induces COX‐2 expression in wild‐type mouse embryo fibroblasts (MEF S/S ) and that the inducibility is reduced in MEF A/A cells in which the phosphorylation site, Ser‐51 in the eIF2α, is replaced with a nonphosphorylatable Ala (S51A). Our data also shows that translational efficiency of COX‐2 is higher in MEF A/A cells than in MEF S/S cells, but not at the late stage of UV‐irradiation. This observation correlates to the translational regulation of COX‐2 binding protein T‐cell‐restricted intracellular antigen 1‐related protein (TIAR) expression, which is reduced in MEF S/S cells but not in MEF A/A cells at 24 hours post‐UV. In addition, our data indicates that newly synthesized COX‐2 protein is more stable in MEF A/A cells than in MEF S/S cells. These results suggest that translation initiation plays a role in a complex and dynamic regulation of COX‐2 expression. By utilizing Ingenuity Pathway Analysis(tm) software, we were able to analyze our results with respect to that of previously published research and deduce a pathway for the translational activation and regulation of COX‐2 expression. This work was supported by National Institutes of Health Grant RO1 CA86926 (to S. W.) and R56 CA086928 (to S. W.).