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Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein and the only known cellular protein to undergo hypusination, a post-translational modification essential for its activity (UniProt P63241). While its name suggests a role in initiation, eIF5A primarily functions during translation elongation, specifically facilitating the synthesis of proteins containing polyproline motifs that would otherwise cause ribosomal stalling (PMID: 23222540). The mRNA encoding eIF5A, particularly the eIF5A2 isoform, is frequently overexpressed in various malignancies, where it acts as a potent oncogene promoting epithelial-mesenchymal transition (EMT), metastasis, and resistance to chemotherapy (PMID: 29153915). Therapeutic strategies targeting eIF5A mRNA, such as antisense oligonucleotides or RNA interference, aim to deplete the pool of eIF5A protein to inhibit the translation of pro-growth and pro-survival factors (PMID: 22508953). However, because eIF5A1 is essential for normal cell viability, achieving isoform-specific targeting or tumor-specific delivery remains a significant challenge in drug development (PMID: 31434155).
Antisense-mediated degradation or RNA interference leading to reduced protein expression of eukaryotic translation initiation factor 5A, thereby inhibiting the translation of polyproline-containing oncogenic proteins.
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