pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation

doi:10.1016/j.canlet.2016.09.009

	pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation
	Wang, Yuxin 4,5; Zhao, Wenting 4,5; Gao, Qiang 4,5; Fan, Li 4,5; Qin, Yanqing 4,5; Zhou, Hu3 ; Li, Min 2; Fang, Jing 1,4,5
刊名	CANCER LETTERS
	2016-12-01
卷号	383 期号:1 页码:1-8
关键词	IKK beta pVHL Ubiquitination
ISSN号	0304-3835
DOI	10.1016/j.canlet.2016.09.009
文献子类	Article
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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
资助项目	National Natural Foundation of China[31470769] ; National Natural Foundation of China[31270829] ; Shanghai Ministry of Science and Technology[16JC1406100] ; Chinese Academy of Sciences[XDA08030300] ; Chinese Academy of Sciences[KFJ-EW-STS-099] ; CAS/SAFEA International Partnership Program for Creative Research Teams[00000000]
WOS关键词	NF-KAPPA-B ; CANCER DEVELOPMENT ; PROTEIN ; KINASE ; CELLS ; ACTIVATION ; LIGASE ; PHOSPHORYLATION ; UBIQUITYLATION ; SENSITIZES
WOS研究方向	Oncology
语种	英语
出版者	ELSEVIER IRELAND LTD
WOS记录号	WOS:000387522600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275788]
专题	分析化学研究室
通讯作者	Fang, Jing
作者单位	1.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China 2.Univ Oklahoma, Dept Surg, Hlth Sci Ctr, Oklahoma City, OK 73104 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 4.Univ Chinese Acad Sci, Beijing, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Food Safety Res, 320 Yueyang Rd, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Yuxin,Zhao, Wenting,Gao, Qiang,et al. pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation[J]. CANCER LETTERS,2016,383(1):1-8.
APA	Wang, Yuxin.,Zhao, Wenting.,Gao, Qiang.,Fan, Li.,Qin, Yanqing.,...&Fang, Jing.(2016).pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation.CANCER LETTERS,383(1),1-8.
MLA	Wang, Yuxin,et al."pVHL mediates K63-linked ubiquitination of IKK beta, leading to IKK beta inactivation".CANCER LETTERS 383.1(2016):1-8.