title: Germline quality control: eEF2K stands guard to eliminate defective oocytes.
abstract: The control of germline quality is critical to reproductive success and survival of a species; however, the mechanisms underlying this process remain unknown. Here, we demonstrate that elongation factor 2 kinase (eEF2K), an evolutionarily conserved regulator of protein synthesis, functions to maintain germline quality and eliminate defective oocytes. We show that disruption of eEF2K in mice reduces ovarian apoptosis and results in the accumulation of aberrant follicles and defective oocytes at advanced reproductive age. Furthermore, the loss of eEF2K in Caenorhabditis elegans results in a reduction of germ cell death and significant decline in oocyte quality and embryonic viability. Examination of the mechanisms by which eEF2K regulates apoptosis shows that eEF2K senses oxidative stress and quickly downregulates short-lived antiapoptotic proteins, XIAP and c-FLIPL by inhibiting global protein synthesis. These results suggest that eEF2K-mediated inhibition of protein synthesis renders cells susceptible to apoptosis and functions to eliminate suboptimal germ cells.
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Hsueh-Ping
authors.initials: HP
authors.lastname: Chu
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Novak
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Zhixian
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Merkin
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Shymkiv
authors.affiliation: Department of Biology, University of Gent, 9000, Gent, Belgium.
authors.forename: Bart P
authors.initials: BP
authors.lastname: Braeckman
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Maxim V
authors.initials: MV
authors.lastname: Dorovkov
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Department of Cell Biology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, 08084, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Clifford
authors.affiliation: Department of Cell Biology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, 08084, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Nagele
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, 04609, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Harrison
authors.affiliation: Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, New Jersey, 08084, USA.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Ellis
authors.affiliation: Department of Pharmacology, Rutgers The State University of New Jersey - Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
authors.forename: Alexey G
authors.initials: AG
authors.lastname: Ryazanov
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D054736:Elongation Factor 2 Kinase / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005854:Germ Cells / Q000473:pathology*; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010053:Ovary / Q000166:cytology / Q000502:physiology; D010766:Phosphorylation; D011786:Quality Control
chemical_list: C517690:Eef2k protein, mouse; D054736:Elongation Factor 2 Kinase; D020169:Caspases