Elongation Factor 2 Kinase Regulation in Cancer Biology

Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent protein kinase that negatively regulates the elongation phase of mRNA translation by phosphorylating elongation factor 2 (eEF2). Under conditions of nutrient deprivation, hypoxia or genotoxic stress, eEF2K is activated by upstream sensors such as AMP-activated protein kinase and calmodulin, while growth-promoting signals conveyed by mammalian target of rapamycin complex 1 (mTORC1) suppress its activity. In cancer, eEF2K contributes to survival during metabolic and environmental stress, modulates the DNA damage response, promotes angiogenesis and supports invasive phenotypes through coordination of signalling networks including PI3K/Akt and STAT3. There is evidence for a context-dependent dual role, whereby eEF2K can both protect tumour cells against hostile microenvironments and, in certain settings, limit excessive proliferation. Its restricted requirement in normal tissues alongside its multifaceted involvement in tumour progression has spurred efforts to target eEF2K therapeutically.

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Elongation Factor 2 Kinase Regulation in Cancer Biology publication trend

The graph below shows the total number of articles in elongation factor 2 kinase regulation in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

eEF2K: An atypical Ser/Thr kinase that phosphorylates elongation factor 2 to inhibit protein synthesis elongation under stress.

eEF2: A GTP-dependent translocase that catalyses ribosomal movement along mRNA during translation elongation.

mTORC1: A central nutrient- and growth factor-sensing kinase complex that promotes protein synthesis and cell growth while inhibiting eEF2K.

Ubiquitin E3 ligase: An enzyme that recognises specific protein substrates, catalysing their ubiquitination and targeting them for proteasomal degradation.

p53: A tumour suppressor protein that orchestrates cell-cycle arrest, DNA repair and apoptosis in response to genomic damage.

PI3K/Akt: A signalling cascade that regulates cell proliferation, survival and metabolism, frequently dysregulated in cancer.

References

1. Design and Characterization of a Novel eEF2K Degrader with Potent Therapeutic Efficacy Against Triple‐Negative Breast Cancer. Advanced Science (2023).
2. The eEF2 kinase coordinates the DNA damage response to cisplatin by supporting p53 activation. Cell Death & Disease (2024).
3. Eukaryotic elongation factor 2 kinase promotes angiogenesis in hepatocellular carcinoma via PI3K/Akt and STAT3. International Journal of Cancer (2019).
4. Eukaryotic Elongation Factor 2 Kinase (eEF2K) in Cancer. Cancers (2017).
5. Stimulation of the AMP-activated Protein Kinase Leads to Activation of Eukaryotic Elongation Factor 2 Kinase and to Its Phosphorylation at a Novel Site, Serine 398*. Journal of Biological Chemistry (2004).
6. The Molecular Mechanism of Eukaryotic Elongation Factor 2 Kinase Activation*. Journal of Biological Chemistry (2014).