NFkappaB activation is associated with its O-GlcNAcylation state under hyperglycemic conditions.
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.
Yang
Won Ho
WH
Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749, Korea.
Park
Sang Yoon
SY
Nam
Hyung Wook
HW
Kim
Do Hyun
DH
Kang
Jeong Gu
JG
Kang
Eun Seok
ES
Kim
Yu Sam
YS
Lee
Hyun Chul
HC
Kim
Kwan Soo
KS
Cho
Jin Won
JW
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*
D016328:NF-kappa B; D008156:Luciferases; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases