NFκB activation is associated with its O -GlcNAcylation state under hyperglycemic conditions
- 11 November 2008
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (45) , 17345-17350
- https://doi.org/10.1073/pnas.0806198105
Abstract
The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification of the NFκB p65 subunit by O -linked N -acetylglucosamine ( O -GlcNAc) has been reported, but the modification site of O -GlcNAc on NFκB p65 and its exact function have not been elucidated. In this work, we show that O -GlcNAcylation of NFκB p65 decreases binding to IκBα and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFκB p65 can be modified with O -GlcNAc, but modification on Thr-352, not Thr-322, is important for transcriptional activation. Our findings suggest that site-specific O -GlcNAcylation may be a reason why NFκB activity increases continuously under hyperglycemic conditions.Keywords
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