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.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3' Untranslated Regions
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Active Transport, Cell Nucleus / drug effects
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Amino Acid Substitution
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Animals
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Base Sequence
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Binding Sites / genetics
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Cell Line
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Cyclooxygenase 2 / biosynthesis
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Cyclooxygenase 2 / genetics*
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Enzyme Induction / drug effects
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Gene Expression Regulation, Enzymologic
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Gene Knockdown Techniques
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / antagonists & inhibitors
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / genetics
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism*
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Humans
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Lipopolysaccharides / pharmacology
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Mice
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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RNA Stability*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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RNA, Small Interfering / genetics
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Rabbits
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
Substances
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3' Untranslated Regions
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Lipopolysaccharides
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RNA, Messenger
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RNA, Small Interfering
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Recombinant Proteins
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)