| First Author | Liu R | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 13 | Pages | 2722-2735.e9 |
| PubMed ID | 34077757 | Mgi Jnum | J:319691 |
| Mgi Id | MGI:6721355 | Doi | 10.1016/j.molcel.2021.05.005 |
| Citation | Liu R, et al. (2021) Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets. Mol Cell 81(13):2722-2735.e9 |
| abstractText | 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) alpha2 to lipid droplets, which is sequentially mediated by AMPK-dependent CHKalpha2 S279 phosphorylation and KAT5-dependent CHKalpha2 K247 acetylation. Importantly, CHKalpha2 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 CHKalpha2 S279 phosphorylation, CHKalpha2 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 CHKalpha2 as a protein kinase in lipolysis and glioblastoma development. |
