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Glyceraldehyde-3-phosphate dehydrogenase regulates cyclooxygenase-2 expression by targeting mRNA stability
Yuki Ikeda1, Ryoichi Yamaji, Kazuhiro Irie
1Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
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.
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