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

Proceedings of the National Academy of Sciences of the United States of America - Tập 105 Số 45 - Trang 17345-17350 - 2008
Won Ho Yang1,2, Sangyoon Park1,2, Hyung Wook Nam3,2, Do Hyun Kim1,2, Jeong Gu Kang1,2, Eun Seok Kang4, Yu Sam Kim5,2,6, Hyun Chul Lee4, Kwan Soo Kim7, Jin Won Cho8,2,6
1Departments of aBiology,; Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea;
2Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea;
3Biochemistry, and; Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea;
4Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea; and
5Biochemistry, and; Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea;; ProteomeTech, Yonsei Dairy Building, Seodaemun-gu, Seoul 120-749, Korea
6ProteomeTech, Yonsei Dairy Building, Seodaemun-gu, Seoul 120-749, Korea
7Chemistry and Center for Bioactive Molecular Hybrids, and
8Departments of aBiology,; Protein Network Research Center, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea;; ProteomeTech, Yonsei Dairy Building, Seodaemun-gu, Seoul 120-749, Korea

Tóm tắt

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.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 105 Số 45

17345-17350

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