Frontiers in Oncology | 卷:9 |
Livin Regulates H2A.XY142 Phosphorylation and Promotes Autophagy in Colon Cancer Cells via a Novel Kinase Activity | |
关键词: Livin; autophagy; colon cancer cells; H2A.X; phosphorylation; | |
DOI : 10.3389/fonc.2019.01233 | |
来源: DOAJ |
【 摘 要 】
Objective: To investigate Livin-mediated regulation of H2A.XY142 phosphorylation via a novel kinase activity and its effect on autophagy in colon cancer cells.Methods: The interaction between Livin and H2A.X was tested by immunoprecipitation. H2A.X–/– HCT116 cells were transfected with human influenza hemagglutinin (HA)-tagged WT or Y142F phospho-dead mutantH2A.X plasmids. GST-tagged recombinant Livin protein was used to perform in vitro pull-down experiment and kinase assay. H2A.X–/–Livin+/+ SW480 cells were co-transfected with H2A.XWT/H2A.XY142F plasmid and LC3 EGFP-tagged plasmid to explore whether H2A.XY142F was involved in Livin-mediated autophagy induced by starvation in colon cancer cells.Results: Co-immunoprecipitation studies confirmed that Livin interacted with H2A.X and that it was phosphorylation dependent. In vitro kinase assay confirmed that Livin could phosphorylate H2A.X. Knockdown of Livin (Livin–/–) in SW480 cells or HCT116 cells canceled the starvation-induced autophagy in colon cancer cells; H2A.X–/–Livin+/+ SW480 cells transfected with H2A.XWT activated autophagy induced by starvation while cells transfected with H2A.XY142F had no significant difference; Livin-H2A.XY142F axis activated autophagy in colon cancer cells through transcriptionally regulating ATG5 and ATG7.Conclusion: Livin promotes autophagy in colon cancer cells via regulating the phosphorylation of H2A.XY142.
【 授权许可】
Unknown