Eukaryotic Translation Elongation Factors in Oncogenesis and Cellular Dynamics

Eukaryotic translation elongation factors orchestrate the delivery of aminoacyl-tRNAs to the ribosomal A-site during protein synthesis, yet their roles extend far beyond housekeeping. Among these, the alpha subunit isoforms eEF1A1 and eEF1A2 have emerged as pivotal regulators of cell fate, cytoskeletal architecture and signal transduction. Aberrant expression of eEF1A2 in non-native tissues drives oncogenic transformation through activation of proliferative pathways, inhibition of apoptosis and promotion of motility. Conversely, eEF1A1 interacts with tumour suppressors to influence apoptotic thresholds and stress responses. The mitochondrial elongation factor TUFM has been implicated in mitochondrial quality control and in the modulation of programmed cell death, linking bioenergetic status to cellular survival. Collectively, these factors interface with major signalling axes—PI3K/AKT, JAK/STAT and TGF-β/SMAD—to coordinate translational output with dynamic changes in the cytoskeleton and gene expression. Their dual roles in canonical translation and non-canonical signalling render them attractive biomarkers and therapeutic targets, offering routes to sensitise cancer cells through small-molecule inhibitors, targeted biologics or modulation of apoptosis and autophagy.

Research from Nature Portfolio

Recent mechanistic studies have elucidated how the marine-derived compound plitidepsin exerts anti-tumour activity by binding directly to eEF1A2. High-resolution molecular modelling identified a binding pocket between domains 1 and 2 of the GTP-bound form. Functional assays demonstrate that plitidepsin disrupts eEF1A2’s role in proliferation and survival, inducing apoptosis in multiple myeloma models. Resistance cell lines with reduced eEF1A2 expression confirm the factor’s status as a primary drug target. Live-cell imaging techniques reveal stable drug–protein complexes, providing a framework for rational design of next-generation elongation factor inhibitors.

Eukaryotic Translation Elongation Factors in Oncogenesis and Cellular Dynamics publication trend

The graph below shows the total number of articles in eukaryotic translation elongation factors in oncogenesis and cellular dynamics across all publications each year (not limited to Nature Index journals).

Technical terms

Eukaryotic translation elongation factor 1 alpha (eEF1A): GTP-dependent mediator of aminoacyl-tRNA delivery to the ribosome, with two mammalian isoforms differing in expression and extra-translational functions.

EEF1A2: Tissue-specific alpha isoform whose abnormal expression confers oncogenic properties by modulating signalling and cytoskeletal dynamics.

Tu translation elongation factor, mitochondrial (TUFM): Mitochondrial GTPase essential for organellar protein synthesis and regulator of programmed cell death pathways.

Epithelial–mesenchymal transition (EMT): Phenotypic switch enabling epithelial cells to acquire migratory and invasive characteristics during cancer progression.

TGF-β/SMAD signalling: Pathway in which TGF-β ligand binding triggers SMAD protein phosphorylation and nuclear translocation to regulate gene expression associated with proliferation, differentiation and EMT.

References

1. Oncogenic activation of EEF1A2 expression: a journey from a putative to an established oncogene. Cellular & Molecular Biology Letters (2024).
2. TUFM in health and disease: exploring its multifaceted roles. Frontiers in Immunology (2024).
3. Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin. Scientific Reports (2016).
4. EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling. British Journal of Cancer (2021).