During nutrient deprivation, cells protect themselves by shutting down energy-demanding processes such as protein synthesis. EFK-1/eEF2K (eukaryotic elongation factor 2 kinase) is a conserved kinase that responds to starvation by inactivating EEF-2/eEF2, the rate-limiting driver of translation elongation, thus blocking mRNA translation to conserve energy. In C. elegans, the eEF2K ortholog
efk-1 is transcriptionally induced in starvation and is essential for L1 starvation survival. However, little is known about the factors that promote starvation survival downstream of
efk-1. Interestingly, Pseudomonas aeruginosa virulence factor ToxA also causes EEF-2 inhibition, which activates the transcription factors (TFs) ZIP-2/bZIP and CEBP-2/CEBPG downstream; additionally, eEF2K also regulates
p53 in cancer cells. Thus, we asked if the TFs
zip-2,
cebp-2, and
cep-1 function in starvation survival downstream of
efk-1. Using the population starvation survival assay, we found that these factors are indeed required for L1 starvation survival. Next, we asked whether these TFs function in the
efk-1 pathway. We found that
efk-1;
zip-2 and
efk-1;
cep-1 double mutants do not exhibit synthetic starvation survival defect compared to single mutants, indicating that these TFs act in the
efk-1 pathway. Next, to characterize the pathways regulated by EFK-1, ZIP-2, and CEP-1 in starvation, we performed gene expression profiling by RNA-seq on wildtype and
efk-1,
zip-2, and
cep-1 null mutants in fed and starved conditions. Consistent with functional data, the transcriptomic profiles of starved
zip-2,
cep-1, or
efk-1 mutants correlate well with each other. Additionally, we found that expression of DNA repair pathways, such as nucleotide excision repair (NER), were elevated in starved wildtype worms, but attenuated in
efk-1,
zip-2, and
cep-1 mutants, suggesting that EFK-1 activates DNA repair during starvation via ZIP-2 and CEP-1. As follow-up, we used the starvation survival assay to confirm that NER factors such as XPA-1 and others are also required for L1 starvation survival. Furthermore, by assaying starvation survival of the
efk-1;
xpa-1 double mutant, we found that
efk-1 and
xpa-1 function in the same pathway. In the future, we plan to confirm the role of EFK-1 in starvation-induced DNA repair by quantifying DNA damage in fed and starved wildtype and
efk-1 mutant worms. Overall, our study has identified a new possible downstream mechanism by which
efk-1/eEF2K promotes starvation stress resistance.