Eukaryotic elongation factor 2 kinase (EEF2K) (EEF2K)

Eukaryotic elongation factor 2 kinase (EEF2K) is a specialized alpha-kinase that regulates the elongation phase of protein translation by phosphorylating eukaryotic elongation factor 2 (eEF2) (PubMed: 23184943). This phosphorylation event reduces the affinity of eEF2 for the ribosome, effectively slowing down protein synthesis to conserve energy during cellular stress, such as hypoxia or nutrient deprivation (UniProt: O00418). In the context of oncology, EEF2K is frequently upregulated and serves as a survival mechanism for cancer cells, contributing to tumor progression and resistance to therapies in breast, pancreatic, and brain cancers (PubMed: 25113395). Beyond its role in cancer, EEF2K has been implicated in neurological disorders like Alzheimer's disease and major depressive disorder due to its influence on synaptic plasticity (PubMed: 30104601). Therapeutic interventions targeting EEF2K include small-molecule inhibitors like A-484954 and nucleic acid-based strategies, such as siRNA-mediated knockdown of EEF2K mRNA, which have shown promise in preclinical models for reducing tumor growth (PubMed: 22351745). While EEF2K is considered a viable target because it is not essential for normal cell survival under non-stressed conditions, potential safety concerns include its impact on cognitive function and cardiovascular homeostasis (PubMed: 28211523).

Other names

Calmodulin-dependent protein kinase IIICaMKIIIeEF-2 kinaseCalcium/calmodulin-dependent eukaryotic elongation factor 2 kinase

EEF2K phosphorylates eukaryotic elongation factor 2 (eEF2) at Thr56, which reduces the affinity of eEF2 for the ribosome, thereby inhibiting the elongation phase of protein synthesis (PubMed: 23184943). Targeting the mRNA via siRNA or antisense oligonucleotides leads to the degradation of the transcript and subsequent reduction in EEF2K protein levels (PubMed: 22351745).