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论文题目: pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation
英文论文题目: pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation
第一作者: Wang, YX; Zhao, WT; Gao, Q; Fan, L; Qin, YQ; Zhou, H; Li, M; Fang, J
英文第一作者: Wang, YX; Zhao, WT; Gao, Q; Fan, L; Qin, YQ; Zhou, H; Li, M; Fang, J
联系作者: Fang, J (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Food Safety Res, 320 Yueyang Rd, Shanghai, Peoples R China.
英文联系作者: Fang, J (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Food Safety Res, 320 Yueyang Rd, Shanghai, Peoples R China.
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发表年度: 2016
卷: 383
期: 1
页码: 1-8
摘要: Nuclear factor (NF)-kappa B is a transcription factor that plays an important role in many biological functions. Regulation of NF-kappa B activity is complicated, and ubiquitination is essential for NF-kappa B activation. Hypoxia can activate NF-kappa B. However, the underlying mechanism remains unclear. pVHL is a tumour suppressor and functions as an adaptor of E3-ligase. In this study, we demonstrated that pVHL inhibits NF-kappa B by mediating K63-ubiquitination of IKK beta, which is dependent on oxygen. We found that pVHL mediates K63-linked ubiquitination of IKK beta, which is an upstream regulator of NF-kappa B. The pVHL-mediated K63-ubiquitination of IKK beta prevents TAK1 binding, which leads to the inhibition of IKK beta phosphorylation and NF-kappa B activation. pVHL-mediated K63-ubiquitination of IKK beta is inhibited under hypoxia. DMOG, which is a specific inhibitor of prolyl hydroxylases, also suppresses K63-ubiquitination of IKK beta. Prolyl hydroxylase (PHD) 1 enhances K63-ubiquitination of imp and inhibits IKK beta phosphorylation. These results suggest a novel function for pVHL in mediating K63-linked ubiquitination of IKK beta, which plays a role in the regulation of IKK/NF-kappa B signalling. The results also provide new insight into the mechanism of NF-kappa B activation through hypoxia.
英文摘要: Nuclear factor (NF)-kappa B is a transcription factor that plays an important role in many biological functions. Regulation of NF-kappa B activity is complicated, and ubiquitination is essential for NF-kappa B activation. Hypoxia can activate NF-kappa B. However, the underlying mechanism remains unclear. pVHL is a tumour suppressor and functions as an adaptor of E3-ligase. In this study, we demonstrated that pVHL inhibits NF-kappa B by mediating K63-ubiquitination of IKK beta, which is dependent on oxygen. We found that pVHL mediates K63-linked ubiquitination of IKK beta, which is an upstream regulator of NF-kappa B. The pVHL-mediated K63-ubiquitination of IKK beta prevents TAK1 binding, which leads to the inhibition of IKK beta phosphorylation and NF-kappa B activation. pVHL-mediated K63-ubiquitination of IKK beta is inhibited under hypoxia. DMOG, which is a specific inhibitor of prolyl hydroxylases, also suppresses K63-ubiquitination of IKK beta. Prolyl hydroxylase (PHD) 1 enhances K63-ubiquitination of imp and inhibits IKK beta phosphorylation. These results suggest a novel function for pVHL in mediating K63-linked ubiquitination of IKK beta, which plays a role in the regulation of IKK/NF-kappa B signalling. The results also provide new insight into the mechanism of NF-kappa B activation through hypoxia.
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学科: Oncology
英文学科: Oncology
影响因子: 6.375
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论文类别: Article
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