Smurf1-mediated Axin Ubiquitination Requires Smurf1 C2 Domain and Is Cell Cycle-dependent

	Smurf1-mediated Axin Ubiquitination Requires Smurf1 C2 Domain and Is Cell Cycle-dependent
	Fei, C; He, XL; Xie, SC; Miao, HF; Zhou, ZL; Li, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2014
卷号	289 期号:20 页码:14170-14177
关键词	Beta-catenin Cell Cycle Protein-Protein Interactions Ubiquitination Wnt Signaling
通讯作者	Li, L (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,lli@sibs.ac.cn
英文摘要	Background: Smurf1 ubiquitinates Axin via K29 poly-ubiquitin chains, and interferes with Wnt/-catenin signaling. Results: The C2 domain of Smurf1 is responsible for interacting with Axin, and Smurf1-mediated Axin ubiquitination attenuates in the G2/M phase of cell cycle. Conclusion: Smurf1-Axin interaction follows a non-canonical pattern and is under the control of cell cycle. Significance: Further clarification of the characteristic of Smurf1-mediated K29-linked poly-ubiquitination of Axin. Previously, Smad ubiquitination regulatory factor 1 (Smurf1)-mediated Lys29 (K29)-linked poly-ubiquitination of Axin has been identified as a novel regulatory process in Wnt/-catenin signaling. In this work, we discovered that the C2 domain of Smurf1 is critical for targeting Axin for ubiquitination. We found that the C2 domain-mediated plasma membrane localization of Smurf1 is required for Axin ubiquitination, and interfering with that disturbs the co-localization of Smurf1 and Axin around the plasma membrane. Moreover, the C2 domain of Smurf1, rather than its WW domains, is involved in Smurf1's interaction with Axin; and the putative PPXY motifs (PY motif) of Axin are not essential for such an interaction, indicating that Smurf1 binds to Axin in a non-canonical way independent of WW-PY interaction. Further, we found that Smurf1-Axin interaction and Axin ubiquitination are attenuated in the G2/M phase of cell cycle, contributing to an increased cell response to Wnt stimulation at that stage. Collectively, we uncovered a dual role of Smurf1 C2 domain, recruiting Smurf1 to membrane for accessing Axin and mediating its interaction with Axin, and that Smurf1-mediated Axin ubiquitination is subjected to the regulation of cell cycle.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	LIGASE SMURF1 ; CATENIN ; PROMOTE ; PATHWAY ; CANCER ; DEGRADATION ; STABILITY ; DISEASE ; PROTEIN ; TARGET
收录类别	SCI
语种	英语
WOS记录号	WOS:000335984600044
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/262]
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,He, XL,Xie, SC,et al. Smurf1-mediated Axin Ubiquitination Requires Smurf1 C2 Domain and Is Cell Cycle-dependent[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(20):14170-14177.
APA	Fei, C,He, XL,Xie, SC,Miao, HF,Zhou, ZL,&Li, L.(2014).Smurf1-mediated Axin Ubiquitination Requires Smurf1 C2 Domain and Is Cell Cycle-dependent.JOURNAL OF BIOLOGICAL CHEMISTRY,289(20),14170-14177.
MLA	Fei, C,et al."Smurf1-mediated Axin Ubiquitination Requires Smurf1 C2 Domain and Is Cell Cycle-dependent".JOURNAL OF BIOLOGICAL CHEMISTRY 289.20(2014):14170-14177.