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

作     者：Na Liu Rui Yang Ying Shi Ling Chen Yating Liu Zuli Wang Shouping Liu Lianlian Ouyang Haiyan Wang Weiwei Lai Chao Mao Min Wang Yan Cheng Shuang Liu Xiang Wang Hu Zhou Ya Cao Desheng Xiao Yongguang Tao Na Liu;Rui Yang;Ying Shi;Ling Chen;Yating Liu;Zuli Wang;Shouping Liu;Lianlian Ouyang;Haiyan Wang;Weiwei Lai;Chao Mao;Min Wang;Yan Cheng;Shuang Liu;Xiang Wang;Hu Zhou;Ya Cao;Desheng Xiao;Yongguang Tao

作者机构：Department of PathologyKey Laboratory of Carcinogenesis and Cancer Invasion(Ministry of Education)Xiangya HospitalCentral South University410078 HunanChina NHC Key Laboratory of Carcinogenesis(Central South University)Cancer Research Institute and School of Basic MedicineCentral South University410078 ChangshaHunanChina Postdoctoral Research WorkstationDepartment of NeurosurgeryXiangya HospitalCentral South University410078 HunanChina Department of OncologyInstitute of Medical SciencesNational Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South University410008 ChangshaHunanChina Xiangya School of Pharmaceutical SciencesCentral South University410078 ChangshaChina Hunan Key Laboratory of Tumor Models and Individualized MedicineHunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung CancerDepartment of Thoracic SurgerySecond Xiangya HospitalCentral South University410011 ChangshaChina Shanghai Institute of Material MedicalChinese Academy of Sciences(CAS)555 Zuchongzhi RoadZhangjiang Hi-Tech Park201203 ShanghaiChina 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2020年第5卷第1期

页      面：670-683页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China[81672991 and 81874139 to S.L.,81872285 to Y.S.,81728014 to Y.T.,81672787 to Y.T.,81672307 to X.W,81772927 to D.X.] the National Basic Research Program of China[2015CB553903 to Y.T.] the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.111-2-12) the Fundamental Research Funds for the Central Universities[2017zzts206 to N.L.]. 

主　　题：cancer residue phosphorylation 

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.