title: NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions.
abstract: The transcription factor NFkappaB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification of the NFkappaB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modification site of O-GlcNAc on NFkappaB p65 and its exact function have not been elucidated. In this work, we show that O-GlcNAcylation of NFkappaB p65 decreases binding to IkappaB alpha and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFkappaB 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 NFkappaB activity increases continuously under hyperglycemic conditions.
authors.affiliation: Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Yang
authors.forename: Sang Yoon
authors.initials: SY
authors.lastname: Park
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Nam
authors.forename: Do Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Jeong Gu
authors.initials: JG
authors.lastname: Kang
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.forename: Yu Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
authors.forename: Kwan Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Cho
mesh_terms: D000107:Acetylation; D000818:Animals; D024202:Electrophoretic Mobility Shift Assay; D006943:Hyperglycemia / Q000378:metabolism*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D008156:Luciferases; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases