Eukaryotic translation initiation factor 5A-1 (K50R mutant) (eIF5A K50R)

Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential for the translation of mRNAs containing specific motifs, such as polyproline sequences, which otherwise cause ribosomal stalling. It is unique as the only known protein to undergo hypusination, a post-translational modification on Lysine 50 (K50) that is required for its biological activity (Park et al., 2010). The K50R mutant is a synthetic variant where this lysine is replaced by arginine, preventing hypusination and creating an inactive form of the protein that can act as a dominant-negative inhibitor. In clinical development, the eIF5A K50R mutant is utilized as a therapeutic payload in the SNS01-T nanoparticle system, designed to treat B-cell malignancies like multiple myeloma and B-cell lymphoma (Mathews and Hershey, 2015). This approach combines the expression of the K50R mutant with siRNAs targeting endogenous eIF5A to suppress the translation of oncogenic proteins like MYC, thereby inducing apoptosis in malignant cells. Additionally, the eIF5A pathway is implicated in viral replication (e.g., HIV-1) and neurodevelopmental disorders, making the K50R mutant a vital tool for studying these pathologies and a template for targeted therapeutic intervention (Fichtman et al., 2019).

Other names

eIF-5A K50ReIF5A1 K50Rnon-hypusinable eIF5AeIF5A-K50R

Dominant-negative inhibition of translation elongation and induction of apoptosis via replacement of functional hypusinated eIF5A with the inactive K50R mutant.