Polyamine-mediated post-transcriptional regulation of COX-2.
Polyamines are involved in various cellular processes including embryonic development, cell growth and cell cycle regulation, apoptosis and carcinogenesis. Growing evidence suggests the importance of RNA processing and stability mediated by oncogenes and tumor suppressor genes in the development of cancer. Polyamines, which are found to be increased in neoplastic cells and tissues compared to normal, bind to RNA to influence its structure and function. Polyamines mediate RNA processing through the spermidine-regulated protein, eIF-5A. To further investigate how polyamines influence RNA expression, we characterized the polyamine-dependent RNA expression of a cancer-related gene, cyclooxygenase-2 (COX-2), which contains eIF-5A consensus binding elements. Depletion of polyamines by DL-alpha-difluoromethylornithine (DFMO) treatment caused an induction of COX-2 mRNA steady-state levels. Polyamines appear to regulate expression of COX-2 by a post-transcriptional mechanism.
Parker
Michele Taylor
MT
Cancer Biology Interdisciplinary Graduate Program, Arizona Cancer Center, The University of Arizona, 1515 N Campbell Avenue, P O Box 245024, Tucson, Arizona 85724, USA.
Gerner
Eugene W
EW
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015317:Biogenic Polyamines / Q000096:biosynthesis / Q000494:pharmacology*; D015152:Blotting, Northern; D018938:Caco-2 Cells; D051546:Cyclooxygenase 2; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008954:Models, Biological; D010448:Peptide Initiation Factors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A
D020413:3' Untranslated Regions; D015317:Biogenic Polyamines; D051546:Cyclooxygenase 2; D000518:Eflornithine; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010448:Peptide Initiation Factors; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C496540:PTGS2 protein, human