title: Glyceraldehyde-3-phosphate dehydrogenase regulates cyclooxygenase-2 expression by targeting mRNA stability.
abstract: Cyclooxygenase (COX)-2 is an inducible inflammatory protein whose expression is partially regulated at the post-transcriptional level. We investigated whether glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds to the AU-rich element (ARE) of COX-2 mRNA for its degradation. Knockdown of GAPDH in hepa1c1c7 cells significantly enhanced COX-2 expressions. Recombinant GAPDH bound to the COX-2 ARE within the first 60 nucleotides of the 3'-UTR via the NAD(+) binding domain. Interestingly, a C151S GAPDH mutant retained binding activity. Confocal microscopy observation revealed that LPS exposure reduced the localization of GAPDH in nuclei. Our results indicate that GAPDH negatively regulates COX-2 by binding to its ARE.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yamaji
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kioka
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
mesh_terms: D020413:3' Untranslated Regions; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)