eEF1A2 (eukaryotic translation elongation factor 1-alpha 2)

Class

Small molecule — marine-derived cyclic depsipeptide (plitidepsin/Aplidin); inhibits eEF1A2, interfering with protein synthesis, triggers mitochondrial cytochrome c release and JNK/caspase-3 activation, inducing apoptosis and G1 cell-cycle arrest

Pathway

Protein synthesis inhibition / mitochondrial apoptosis

Eukaryotic translation elongation factor 1-alpha 2 (eEF1A2) is a protein that helps ribosomes build new proteins by shuttling amino acid-loaded transfer RNAs to the growing peptide chain. It is normally expressed mainly in muscle, heart, and neurons, but many cancer cells reactivate or overexpress it, using the extra protein-synthesis capacity to sustain rapid growth and to suppress programmed cell death (apoptosis). Because eEF1A2 also has functions beyond translation, including interactions with proteins that regulate the cell cycle and cell survival, blocking it can simultaneously slow protein production and destabilize the signals that keep cancer cells alive. Small molecules that bind eEF1A2 exploit this dependency: by inhibiting its activity, they halt protein synthesis in cells that rely heavily on it, arrest the cell cycle at the G1 phase, and trigger stress signals that converge on the mitochondria, ultimately activating the cell's intrinsic apoptosis machinery. This mechanism is of interest broadly in oncology, particularly in cancers of the blood and lymphatic system where malignant cells often show high translational activity and dependence on this elongation factor for survival.