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

2008; National Academy of Sciences; Volume: 105; Issue: 45 Linguagem: Inglês

10.1073/pnas.0806198105

1091-6490

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

Immune Response and Inflammation

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.