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Livin Regulates H2A.X Y142 Phosphorylation and Promotes Autophagy in Colon Cancer Cells via a Novel Kinase Activity.
- Source :
-
Frontiers in oncology [Front Oncol] 2019 Nov 14; Vol. 9, pp. 1233. Date of Electronic Publication: 2019 Nov 14 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- Objective: To investigate Livin-mediated regulation of H2A.X <superscript>Y142</superscript> 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.X <superscript>WT</superscript> /H2A.X <superscript>Y142F</superscript> plasmid and LC3 EGFP-tagged plasmid to explore whether H2A.X <superscript>Y142F</superscript> 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.X <superscript>WT</superscript> activated autophagy induced by starvation while cells transfected with H2A.X <superscript>Y142F</superscript> had no significant difference; Livin-H2A.X <superscript>Y142F</superscript> 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.X <superscript>Y142</superscript> .<br /> (Copyright © 2019 Ge, Liu, Cui and Li.)
Details
- Language :
- English
- ISSN :
- 2234-943X
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Frontiers in oncology
- Publication Type :
- Academic Journal
- Accession number :
- 31799193
- Full Text :
- https://doi.org/10.3389/fonc.2019.01233