NFκB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions

Ho Yang Won, Yoon Park Sang, Wook Nam Hyung, Hyun Kim Do, Gu Kang Jeong, Seok Kang Eun, Sam Kim Yu, Chul Lee Hyun, Soo Kim Kwan, Jin Won Cho

Research output: Contribution to journalArticle

135 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)17345-17350
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number45
DOIs
Publication statusPublished - 2008 Nov 11

All Science Journal Classification (ASJC) codes

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