The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties

doi:10.1038/s41392-020-00249-w

	The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties
	Liu, Na 1,2,3,4,5; Yang, Rui 2,3,4,5; Shi, Ying 2,3,4,5; Chen, Ling 2,3,4,5; Liu, Yating 2,3,4,5; Wang, Zuli 2,3,4,5; Liu, Shouping 2,3,4,5; Ouyang, Lianlian 6; Wang, Haiyan 2,3,4,5; Lai, Weiwei 2,3,4,5
刊名	SIGNAL TRANSDUCTION AND TARGETED THERAPY
	2020-09-30
卷号	5 期号:1 页码:14
ISSN号	2095-9907
DOI	10.1038/s41392-020-00249-w
通讯作者	Xiao, Desheng(xdsh96@21cn.com) ; Tao, Yongguang(taoyong@csu.edu.cn)
英文摘要	Posttranslational modifications (PTMs) of proteins, including chromatin modifiers, play crucial roles in the dynamic alteration of various protein properties and functions including stem-cell properties. However, the roles of Lymphoid-specific helicase (LSH), a DNA methylation modifier, in modulating stem-like properties in cancer are still not clearly clarified. Therefore, exploring PTMs modulation of LSH activity will be of great significance to further understand the function and activity of LSH. Here, we demonstrate that LSH is capable to undergo PTMs, including methylation and phosphorylation. The arginine methyltransferase PRMT5 can methylate LSH at R309 residue, meanwhile, LSH could as well be phosphorylated by MAPK1 kinase at S503 residue. We further show that the accumulation of phosphorylation of LSH at S503 site exhibits downregulation of LSH methylation at R309 residue, which eventually promoting stem-like properties in lung cancer. Whereas, phosphorylation-deficient LSH S503A mutant promotes the accumulation of LSH methylation at R309 residue and attenuates stem-like properties, indicating the critical roles of LSH PTMs in modulating stem-like properties. Thus, our study highlights the importance of the crosstalk between LSH PTMs in determining its activity and function in lung cancer stem-cell maintenance.
资助项目	National Natural Science Foundation of China[81672991] ; National Natural Science Foundation of China[81874139] ; National Natural Science Foundation of China[81872285] ; National Natural Science Foundation of China[81728014] ; National Natural Science Foundation of China[81672787] ; National Natural Science Foundation of China[81672307] ; National Natural Science Foundation of China[81772927] ; National Basic Research Program of China[2015CB553903] ; Overseas Expertise Introduction Project for Discipline Innovation (111 Project)[111-2-12] ; Fundamental Research Funds for the Central Universities[2017zzts206]
WOS关键词	PROTEIN ARGININE METHYLTRANSFERASES ; SNF2 FAMILY-MEMBER ; POSTTRANSLATIONAL MODIFICATION ; SNF2-LIKE GENE ; SELF-RENEWAL ; LSH ; EXPRESSION ; APOPTOSIS ; COMPLEX ; CELLS
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
语种	英语
出版者	SPRINGERNATURE
WOS记录号	WOS:000574260600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291282]
专题	中国科学院上海药物研究所
通讯作者	Xiao, Desheng; Tao, Yongguang
作者单位	1.Cent South Univ, Xiangya Hosp, Dept Neurosurg, Postdoctoral Res Workstat, Changsha 410078, Hunan, Peoples R China 2.Xiangya Hosp, Dept Pathol, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha 410078, Hunan, Peoples R China 3.Cent South Univ, Changsha 410078, Hunan, Peoples R China 4.Cent South Univ, Canc Res Inst, NHC Key Lab Carcinogenesis, Changsha 410078, Hunan, Peoples R China 5.Cent South Univ, Sch Basic Med, Changsha 410078, Hunan, Peoples R China 6.Cent South Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Dept Oncol,Inst Med Sci, Changsha 410008, Hunan, Peoples R China 7.Cent South Univ, Xiangya Sch Pharmaceut Sci, Changsha 410078, Peoples R China 8.Cent South Univ, Xiangya Hosp 2, Dept Thorac Surg, Hunan Key Lab Tumor Models & Individualized Med, Changsha 410011, Peoples R China 9.Cent South Univ, Xiangya Hosp 2, Dept Thorac Surg, Hunan Key Lab Early Diag & Precis Therapy Lung Ca, Changsha 410011, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Liu, Na,Yang, Rui,Shi, Ying,et al. The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2020,5(1):14.
APA	Liu, Na.,Yang, Rui.,Shi, Ying.,Chen, Ling.,Liu, Yating.,...&Tao, Yongguang.(2020).The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties.SIGNAL TRANSDUCTION AND TARGETED THERAPY,5(1),14.
MLA	Liu, Na,et al."The cross-talk between methylation and phosphorylation in lymphoid-specific helicase drives cancer stem-like properties".SIGNAL TRANSDUCTION AND TARGETED THERAPY 5.1(2020):14.