Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/beta-Catenin Signaling

	Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/beta-Catenin Signaling
	Fei, C; Li, ZF; Li, C; Chen, YL; Chen, ZC; He, XL; Mao, L; Wang, X; Zeng, R; Li, L
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2013
卷号	33 期号:20 页码:4095-4105
通讯作者	Li, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai, Peoples R China.,lli@sibs.ac.cn
英文摘要	Ubiquitination plays important and diverse roles in modulating protein functions. As a C2-WW-HECT-type ubiquitin ligase, Smad ubiquitination regulatory factor 1 (Smurf1) commonly serves to regulate ubiquitin-dependent protein degradation in a number of signaling pathways. Here, we report a novel function of Smurf1 in regulating Wnt/beta-catenin signaling through targeting axin for nonproteolytic ubiquitination. Our data unambiguously demonstrate that Smurf1 ubiquitinates axin through Lys 29 (K29)-linked polyubiquitin chains. Unexpectedly, Smurf1-mediated axin ubiquitination does not lead to its degradation but instead disrupts its interaction with the Wnt coreceptors LRP5/6, which subsequently attenuates Wnt-stimulated LRP6 phosphorylation and represses Wnt/beta-catenin signaling. The inhibitory function of Smurf1 on Wnt/beta-catenin signaling is further evidenced by analysis with Smurf1 knockout murine embryonic fibroblasts. We next identified K789 and K821 in axin as the ubiquitination sites by Smurf1. Consistently, Smurf1 could neither disrupt the interaction of an axin(K789/821R) double mutant with LRP5/6 nor attenuate the phosphorylation of LRP6 in axin(K789/821R)-expressing cells. Collectively, our studies uncover Smurf1 as a new regulator for the Wnt/beta-catenin signaling pathway via modulating the activity of axin.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	E3 UBIQUITIN LIGASE ; MASS-SPECTROMETRY ; CELL POLARITY ; DEGRADATION ; PROTEIN ; SMURF1 ; PHOSPHORYLATION ; PATHWAY ; DISEASE ; TARGETS
收录类别	SCI
语种	英语
WOS记录号	WOS:000324912000012
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/462]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Fei, C,Li, ZF,Li, C,et al. Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/beta-Catenin Signaling[J]. MOLECULAR AND CELLULAR BIOLOGY,2013,33(20):4095-4105.
APA	Fei, C.,Li, ZF.,Li, C.,Chen, YL.,Chen, ZC.,...&Li, L.(2013).Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/beta-Catenin Signaling.MOLECULAR AND CELLULAR BIOLOGY,33(20),4095-4105.
MLA	Fei, C,et al."Smurf1-Mediated Lys29-Linked Nonproteolytic Polyubiquitination of Axin Negatively Regulates Wnt/beta-Catenin Signaling".MOLECULAR AND CELLULAR BIOLOGY 33.20(2013):4095-4105.