title: Sodium selenite-induced activation of DAPK promotes autophagy in human leukemia HL60 cells.
abstract: Autophagy has been suggested as a possible mechanism for non-apoptotic death despite evidence from many species that autophagy represents a survival strategy of cells under stress. From our previous findings that supranutritional doses of sodium selenite induced apoptosis in human leukemia cells, now we show autophagic cell death occurred after selenite exposure in HL60, suggested an alternative mechanism for the potential therapeutic properties of selenite. Additionally, Death-associated Protein Kinase (DAPK) performed a significantly increased expression during this process, concomitantly with gradually decreased phosphorylation at Ser(308). We further reveal that the up-regulation of DAPK which depends on selenite-activated ERK had no effect on autophagy. However, activation of DAPK via PP2A-mediated dephosphorylation at Ser(308) serves as a new strategy for autophagy induction. In conclusion, these results indicate that PP2A-mediated activated DAPK sensitizes HL60 cells to selenite, ultimately triggers autophagic cell death pathway to commit cell demise.
authors.affiliation: National Laboratory of Medical Molecular Biology; Institute of Basic Medicine Sciences & School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D064550:Death-Associated Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D018038:Sodium Selenite / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D064550:Death-Associated Protein Kinases; D018038:Sodium Selenite