Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals

doi:10.7554/eLife.15690

	Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals
	Fu, Lin 1; Wu, Hailong 1; Cheng, Steven Y.2; Gao, Daming 1; Zhang, Lei1,3 ; Zhao, Yun1,3
	2016-05-05
发表期刊	ELIFE (IF:6.4[JCR-2023],7.2[5-Year])
ISSN	2050-084X
卷号	5
发表状态	已发表
DOI	10.7554/eLife.15690
摘要	Hedgehog signaling plays very important roles in development and cancers. Vertebrates have three transcriptional factors, Gli1, Gli2 and Gli3. Among them, Gli3 is a very special transcriptional factor which closely resembles Cubitus interruptus (Ci, in Drosophila) structurally and functionally as a 'double agent' for Shh target gene expression. Here we show that Gli3 full-length, but not the truncated form, can be methylated at K436 and K595. This methylation is specifically catalyzed by Set7, a lysine methyltransferase (KMT). Methylation at K436 and K595 respectively increases the stability and DNA binding ability of Gli3, resulting in an enhancement of Shh signaling activation. Furthermore, functional experiments indicate that the Gli3 methylation contributes to the tumor growth and metastasis in non-small cell lung cancer in vitro and in vivo. Therefore, we propose that Set7 mediated methylation is a novel PTM of Gli3, which positively regulates the transactivity of Gli3 and the activation of Shh signaling.
收录类别	SCI
语种	英语
资助项目	"Strategic Priority Research Program" of the Chinese Academy of Sciences[XDB19020104]
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS类目	Biology
WOS记录号	WOS:000379687200001
出版者	ELIFE SCIENCES PUBLICATIONS LTD
WOS关键词	LYSINE METHYLATION ; PROTEIN ; METHYLTRANSFERASE ; PHOSPHORYLATION ; CANCER ; IDENTIFICATION ; TRANSCRIPTION ; SPECIFICITY ; REPRESSOR ; KINASE
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/1842
专题	生命科学与技术学院_特聘教授组_赵允组生命科学与技术学院_特聘教授组_张雷组
通讯作者	Zhao, Yun
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci,CAS Ctr Excellence Mol Cell Sci, Innovat Ctr Cell Signaling Network,Inst Biochem &, State Key Lab Cell Biol,Shanghai Inst Biol Sci, Shanghai, Peoples R China 2.Nanjing Med Univ, Sch Basic Med Sci, Dept Dev Genet, Nanjing, Jiangsu, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Fu, Lin,Wu, Hailong,Cheng, Steven Y.,et al. Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals[J]. ELIFE,2016,5.
APA	Fu, Lin,Wu, Hailong,Cheng, Steven Y.,Gao, Daming,Zhang, Lei,&Zhao, Yun.(2016).Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals.ELIFE,5.
MLA	Fu, Lin,et al."Set7 mediated Gli3 methylation plays a positive role in the activation of Sonic Hedgehog pathway in mammals".ELIFE 5(2016).