@article{0cdc3659a77142ae8609e720d53333d8,
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.",
author = "Chu, {Hsueh Ping} and Yi Liao and Novak, {James S.} and Zhixian Hu and Merkin, {Jason J.} and Yuriy Shymkiv and Braeckman, {Bart P.} and Dorovkov, {Maxim V.} and Alexandra Nguyen and Clifford, {Peter M.} and Nagele, {Robert G.} and Harrison, {David E.} and Ellis, {Ronald E.} and Ryazanov, {Alexey G.}",
note = "Funding Information: We are grateful to E. Shor for many helpful suggestions on the manuscript. We would like to thank E. White for her discussions on the TNF-α-induced apoptosis pathway, J.L. Tilly and H.J. Lee for their expertise regarding in vitro culture of granulosa cells, and K. Schindler for reagents and her expertise regarding in vitro culture of oocytes. Some C. elegans strains were provided by the Caenorhabditis Genetics Center (CGC), which is funded by the National Institutes of Health (NIH) Office of Research Infrastructure Programs (P40 OD010440); other strains were graciously provided by M.C. Soto. We would like to thank C. Rongo and A. Singson for providing access to their C. elegans RNAi libraries and B.D. Grant for technical expertise regarding C. elegans immunostaining. This work was supported by NIH grants: R01GM57300, R01CA81102, R01AG19890, RC1AI078513, R03TW008217, R21AG042870 (A.G.R.), and R01 GM085282 (R.E.E.). A.G.R. is the founder of Longevica Pharmaceuticals, a company involved in the development of eEF2K inhibitors. ",
year = "2014",
month = mar,
day = "10",
doi = "10.1016/j.devcel.2014.01.027",
language = "English (US)",
volume = "28",
pages = "561--572",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",
}