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Signal transduction and targeted therapy
09 30, 2020;5 (1): 197.

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

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
Author Information
  1. Na Liu: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  2. Rui Yang: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  3. Ying Shi: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  4. Ling Chen: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  5. Yating Liu: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  6. Zuli Wang: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  7. Shouping Liu: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  8. Lianlian Ouyang: Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
  9. Haiyan Wang: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  10. Weiwei Lai: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  11. Chao Mao: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  12. Min Wang: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  13. Yan Cheng: Xiangya School of Pharmaceutical Sciences, Central South University, 410078, Changsha, China.
  14. Shuang Liu: Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
  15. Xiang Wang: Hunan Key Laboratory of Tumor Models and Individualized Medicine; Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, 410011, Changsha, China.
  16. Hu Zhou: Shanghai Institute of Material Medical, Chinese Academy of Sciences (CAS), 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, 201203, Shanghai, China.
  17. Ya Cao: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China.
  18. Desheng Xiao: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China. xdsh96@21cn.com.
  19. Yongguang Tao: Department of Pathology, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Xiangya Hospital; Central South University, 410078, Hunan, China. taoyong@csu.edu.cn.
PMID: 32994405 DOI: 10.1038/s41392-020-00249-w

Abstract

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.

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MeSH Term

Animals
Cell Line, Tumor
DNA Helicases
Female
Humans
Lung Neoplasms
Methylation
Mice
Mice, Nude
Neoplasm Proteins
Neoplastic Stem Cells
Phosphorylation

Chemicals

Neoplasm Proteins
DNA Helicases
HELLS protein, human
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 4

Word Cloud

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