The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the ad...The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.展开更多
O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） me...O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.展开更多
据《Lancet》2000年355卷第9214期报道 高雪病(Caucher s disease,一种先天性代谢障碍性疾病)的现代治疗中给予静脉内注射葡萄糖脑苷脂酶,以降低溶酶体的葡萄糖脑苷脂积蓄。降低葡萄糖脑苷脂的生物合成应减少这些基质的积蓄。英国剑桥...据《Lancet》2000年355卷第9214期报道 高雪病(Caucher s disease,一种先天性代谢障碍性疾病)的现代治疗中给予静脉内注射葡萄糖脑苷脂酶,以降低溶酶体的葡萄糖脑苷脂积蓄。降低葡萄糖脑苷脂的生物合成应减少这些基质的积蓄。英国剑桥大学医学部T.Cox教授等观察了COT918(N-butyldeoxyno-jirimycin),一种葡萄糖转换酶抑制剂。展开更多
文摘The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.
基金supported by the grants from the National Program on Key Basic Research Project (Nos. 2013CB910300 and 2012CB910300 to H.P.)the International Science and Technology Cooperation Program of China (No. 2015DFA31680)+2 种基金the One Thousand Young Talent Program (to H.P.)the State Key Laboratory of Proteomics (No. SKLP-O201303 to C.Y.)the National Natural Science Foundation of China (No. 31371433 to H.P.)
文摘O-GlcNAcylation is an important post-translational modification and has been implicated in many fundamental cellular processes. Recent studies showed that O-linked N-acetylglucosamine （GlcNAc） transferase （OGT） mediated O-GlcNAcylation of histone H2B Ser 112 （H2B S 112 GlcNAcylation） plays an important role in gene transcription. However, the role of this histone modification in DNA damage response has not been studied yet. In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress- inducing agents. OGT mediated H2B Sl12 GlcNAcylation increased locally upon the induction of double-strand breaks （DSBs）, and depletion of OGT or overexpression of H2B S 112A mutant impaired homologous recombination （HR） and nonhomologous end-joining （NHEJ）. Mechanistically, H2B Sl12 GlcNAcylation could bind Nijmegen breakage syndrome 1 （NBS1） and regulate NBS1 foci for- mation. Taken together, our results demonstrate a new function of histone O-GlcNAcylation in DNA damage response （DDR）.
文摘据《Lancet》2000年355卷第9214期报道 高雪病(Caucher s disease,一种先天性代谢障碍性疾病)的现代治疗中给予静脉内注射葡萄糖脑苷脂酶,以降低溶酶体的葡萄糖脑苷脂积蓄。降低葡萄糖脑苷脂的生物合成应减少这些基质的积蓄。英国剑桥大学医学部T.Cox教授等观察了COT918(N-butyldeoxyno-jirimycin),一种葡萄糖转换酶抑制剂。
