Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling

doi:10.1016/j.devcel.2015.05.016

	Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling
	Zhou, Zizhang 1,2; Yao, Xia 1,2; Li, Shuang 3; Xiong, Yue 5; Dong, Xiaohua 1,2; Zhao, Yun5,6 ; Jiang, Jin 3,4; Zhang, Qing 1,2
	2015-07-06
发表期刊	DEVELOPMENTAL CELL (IF:10.7[JCR-2023],11.5[5-Year])
ISSN	1534-5807
卷号	34 期号:1 页码:58-72
发表状态	已发表
DOI	10.1016/j.devcel.2015.05.016
摘要	Hedgehog (Hh) signaling plays essential roles in animal development and tissue homeostasis, and its misregulation causes congenital diseases and cancers. Regulation of the ubiquitin/proteasome-mediated proteolysis of Ci/Gli transcription factors is central to Hh signaling, but whether deubiquitinase is involved in this process remains unknown. Here, we show that Hh stimulates the binding of a ubiquitin-specific protease Usp7 to Ci, which positively regulates Hh signaling activity through inhibiting Ci ubiquitination and degradation mediated by both Slimb-Cul1 and Hib-Cul3 E3 ligases. Furthermore, we find that Usp7 forms a complex with GMP-synthetase (GMPS) to promote Hh pathway activity. Finally, we show that the mammalian counterpart of Usp7, HAUSP, positively regulates Hh signaling by modulating Gli ubiquitination and stability. Our findings reveal a conserved mechanism by which Ci/Gli is stabilized by a deubiquitination enzyme and identify Usp7/HUASP as a critical regulator of Hh signaling and potential therapeutic target for Hh-related cancers.
收录类别	SCI
语种	英语
资助项目	Welch Foundation[I-1603]
WOS研究方向	Cell Biology ; Developmental Biology
WOS类目	Cell Biology ; Developmental Biology
WOS记录号	WOS:000357649300007
出版者	CELL PRESS
WOS关键词	TARGETS CUBITUS-INTERRUPTUS ; UBIQUITIN-SPECIFIC PROTEASE ; GMP-SYNTHETASE ; TRANSCRIPTIONAL ACTIVATOR ; REPRESSOR FORMS ; SONIC HEDGEHOG ; KINASE-A ; DEGRADATION ; PHOSPHORYLATION ; SUPPRESSOR
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2181
专题	生命科学与技术学院_特聘教授组_赵允组
通讯作者	Jiang, Jin
作者单位	1.Nanjing Univ, Model Anim Res Ctr, State Key Lab Pharmaceut Biotechnol, Nanjing 210061, Jiangsu, Peoples R China 2.Nanjing Univ, Model Anim Res Ctr, MOE Key Lab Model Anim Dis Study, Nanjing 210061, Jiangsu, Peoples R China 3.Univ Texas SW Med Ctr Dallas, Dept Dev Biol, Dallas, TX 75390 USA 4.Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol,Innovat Ctr Cell Signalin, Shanghai 200031, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Zizhang,Yao, Xia,Li, Shuang,et al. Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling[J]. DEVELOPMENTAL CELL,2015,34(1):58-72.
APA	Zhou, Zizhang.,Yao, Xia.,Li, Shuang.,Xiong, Yue.,Dong, Xiaohua.,...&Zhang, Qing.(2015).Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling.DEVELOPMENTAL CELL,34(1),58-72.
MLA	Zhou, Zizhang,et al."Deubiquitination of Ci/Gli by Usp7/HAUSP Regulates Hedgehog Signaling".DEVELOPMENTAL CELL 34.1(2015):58-72.