Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans PMID: 39966347

ADC Targets in Oncology

2026-04-10

Eukaryotic Elongation Factor 2 Kinase EFK-1/eEF2K promotes starvation resistance by preventing oxidative damage in C. elegans

Nat Commun. 2025 Feb 18;16(1):1752. doi: 10.1038/s41467-025-56766-1.

Junran Yan ¹ ² ³ ⁴ , Forum Bhanshali ¹ ³ ⁵ ⁶ , Chiaki Shuzenji ¹ ² ³ ⁵ , Tsultrim T Mendenhall ⁷ , Shane K B Taylor ¹ ² ³ ⁵ , Glafira Ermakova ¹ ² ³ ⁵ , Xuanjin Cheng ¹ ³ ⁵ ⁸ , Pamela Bai ¹ ² ³ ⁵ , Gahan Diwan ¹ ³ ⁹ , Donna Seraj ¹ ³ ⁵ , Joel N Meyer ¹⁰ , Poul H Sorensen ¹¹ ¹² , Jessica H Hartman ⁷ , Stefan Taubert ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷

Affiliations

1. Centre for Molecular Medicine and Therapeutics, The University of British Columbia, 950 W 28 th Ave, Vancouver, BC, V5Z 4H4, Canada.
2. Edwin S.H. Leong Centre for Healthy Aging, The University of British Columbia, 117-2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
3. British Columbia Children's Hospital Research Institute, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
4. Graduate Program in Cell & Developmental Biology, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
5. Department of Medical Genetics, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada.
6. Catalera BioSolutions, 199 W 6th Ave, Vancouver, BC, V5Y 1K3, Canada.
7. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC, 29425, USA.
8. Canada's Michael Smith Genome Sciences Centre, 570 W 7th Ave, Vancouver, BC, V5Z 4S6, Canada.
9. Department of Biology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
10. Nicholas School of the Environment, Duke University, Durham, NC, 27708-0328, USA.
11. Department of Pathology and Laboratory Medicine, University of British Columbia, 675 W 10th Ave, Vancouver, BC, V6T 1Z4, Canada.
12. Department of Molecular Oncology, BC Cancer Research Institute, 675 W 10th Ave, Vancouver, BC, V5Z 1L3, Canada.
13. Centre for Molecular Medicine and Therapeutics, The University of British Columbia, 950 W 28 th Ave, Vancouver, BC, V5Z 4H4, Canada. [email protected].
14. Edwin S.H. Leong Centre for Healthy Aging, The University of British Columbia, 117-2194 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. [email protected].
15. British Columbia Children's Hospital Research Institute, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. [email protected].
16. Graduate Program in Cell & Developmental Biology, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. [email protected].
17. Department of Medical Genetics, The University of British Columbia, 950 W 28th Ave, Vancouver, BC, V5Z 4H4, Canada. [email protected].

Abstract

Cells and organisms frequently experience starvation. To survive, they mount an evolutionarily conserved stress response. A vital component in the mammalian starvation response is eukaryotic elongation factor 2 (eEF2) kinase (eEF2K), which suppresses translation in starvation by phosphorylating and inactivating the translation elongation driver eEF2. C. elegans EFK-1/eEF2K phosphorylates EEF-2/eEF2 on a conserved residue and is required for starvation survival, but how it promotes survival remains unclear. Surprisingly, we found that eEF2 phosphorylation is unchanged in starved C. elegans and EFK-1's kinase activity is dispensable for starvation survival, suggesting that efk-1 promotes survival via a noncanonical pathway. We show that efk-1 upregulates transcription of DNA repair pathways, nucleotide excision repair (NER) and base excision repair (BER), to promote starvation survival. Furthermore, efk-1 suppresses oxygen consumption and ROS production in starvation to prevent oxidative stress. Thus, efk-1 enables starvation survival by protecting Animals from starvation-induced oxidative damage through an EEF-2-independent pathway.