Page 34 - ebook

[A. Biochemistry/Molecular Biology] A-17

Choline kinase alpha 2 acts as a protein kinase to promote

lipolysis of lipid droplets

Su Hwan Park¹, Jong-Ho Lee¹,²*

¹Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Korea, ²Department of

Biological Sciences, Dong-A University, Busan 49315, Korea

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.