AUTHOR=Ge Yang , Liu Bao-lin , Cui Jun-peng , Li Shu-qiang 

TITLE=Livin Regulates H2A.XY142 Phosphorylation and Promotes Autophagy in Colon Cancer Cells via a Novel Kinase Activity

JOURNAL=Frontiers in Oncology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2019.01233

DOI=10.3389/fonc.2019.01233

ISSN=2234-943X

ABSTRACT=<p><bold>Objective:</bold> To investigate Livin-mediated regulation of H2A.X<sup>Y142</sup> phosphorylation via a novel kinase activity and its effect on autophagy in colon cancer cells.</p><p><bold>Methods:</bold> 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 <italic>in vitro</italic> pull-down experiment and kinase assay. H2A.X–/–Livin+/+ SW480 cells were co-transfected with H2A.X<sup>WT</sup>/H2A.X<sup>Y142F</sup> plasmid and LC3 EGFP-tagged plasmid to explore whether H2A.X<sup>Y142F</sup> was involved in Livin-mediated autophagy induced by starvation in colon cancer cells.</p><p><bold>Results:</bold> Co-immunoprecipitation studies confirmed that Livin interacted with H2A.X and that it was phosphorylation dependent. <italic>In vitro</italic> 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.X<sup>WT</sup> activated autophagy induced by starvation while cells transfected with H2A.X<sup>Y142F</sup> had no significant difference; Livin-H2A.X<sup>Y142F</sup> axis activated autophagy in colon cancer cells through transcriptionally regulating <italic>ATG5</italic> and <italic>ATG7</italic>.</p><p><bold>Conclusion:</bold> Livin promotes autophagy in colon cancer cells via regulating the phosphorylation of H2A.X<sup>Y142</sup>.</p>