2. Academic Validation
  3. Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets

Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets

  • Mol Cell. 2021 Jul 1;81(13):2722-2735.e9. doi: 10.1016/j.molcel.2021.05.005.
Rui Liu 1,  Jong-Ho Lee 2,  Jingyi Li 3,  Rilei Yu 4,  Lin Tan 5,  Yan Xia 6,  Yanhua Zheng 6,  Xue-Li Bian 7,  Philip L Lorenzi 5,  Qianming Chen 8,  Zhimin Lu 9
Affiliations

Affiliations

  • 1 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310029, China; State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China. Electronic address: liurui_scu@hotmail.com.
  • 2 Department of Health Sciences, The Graduate School of Dong-A University, Busan, 49315, Republic of Korea; Department of Biological Sciences, Dong-A University, Busan 49315, Republic of Korea.
  • 3 The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan, 610051, China.
  • 4 Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, Shandong 266003, China.
  • 5 The Proteomics and Metabolomics Core Facility, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
  • 6 Department of Neuro-Oncology and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
  • 7 The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266071, China.
  • 8 Stomatology Hospital, School of Stomatology, Cancer Center, Zhejiang University School of Medicine, and Key Laboratory of Oral Biomedical Research of Zhejiang Province, Clinical Research Center of Oral Diseases of Zhejiang Province, Hangzhou, 310006, Zhejiang, China. Electronic address: qmchen@zju.edu.cn.
  • 9 Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, 310029, China; Zhejiang University Cancer Center, Hangzhou, 310029, China. Electronic address: zhiminlu@zju.edu.cn.
PMID: 34077757 DOI: 10.1016/j.molcel.2021.05.005
Abstract

Lipid droplets are important for Cancer cell growth and survival. However, the mechanism underlying the initiation of lipid droplet lipolysis is not well understood. We demonstrate here that glucose deprivation induces the binding of choline kinase (CHK) α2 to lipid droplets, which is sequentially mediated by AMPK-dependent CHKα2 S279 phosphorylation and KAT5-dependent CHKα2 K247 acetylation. Importantly, CHKα2 with altered catalytic domain conformation functions as a protein kinase and phosphorylates PLIN2 at Y232 and PLIN3 at Y251. The phosphorylated PLIN2/3 dissociate from lipid droplets and are degraded by Hsc70-mediated Autophagy, thereby promoting lipid droplet lipolysis, fatty acid oxidation, and brain tumor growth. In addition, levels of CHKα2 S279 phosphorylation, CHKα2 K247 acetylation, and PLIN2/3 phosphorylation are positively correlated with one another in human glioblastoma specimens and are associated with poor prognosis in glioblastoma patients. These findings underscore the role of CHKα2 as a protein kinase in lipolysis and glioblastoma development.

Keywords

AMPK; KAT5; PLIN2/3; acetylation; autophagy; choline kinase; lipid droplet; lipolysis; phosphorylation; tumorigenesis.

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