Eukaryotic translation initiation factor 5A-1 (eIF5A1)

Eukaryotic translation initiation factor 5A-1 (eIF5A1) is a highly conserved protein essential for cell viability and is the only known protein to undergo hypusination, a unique post-translational modification [1, 2]. Although originally identified as an initiation factor, its primary role is as a translation elongation factor that facilitates the synthesis of proteins containing polyproline motifs by resolving ribosomal stalling [2, 7]. Beyond translation, eIF5A1 is involved in mRNA nuclear export, mRNA decay, and the regulation of apoptosis and mitochondrial function [2, 11]. In disease, eIF5A1 is frequently overexpressed in various malignancies, including pancreatic, lung, and colorectal cancers, where it promotes tumor growth and metastasis [3, 4]. It also serves as a critical host cofactor for the replication of viruses such as HIV-1 and is implicated in the pathogenesis of type 2 diabetes and inflammatory conditions [1, 3]. Therapeutic targeting of eIF5A1 primarily focuses on inhibiting the hypusination pathway using small molecules like GC7 (a DHPS inhibitor) or iron chelators like ciclopirox (a DOHH inhibitor) [7, 9]. However, the essential nature of eIF5A1 for normal cell growth presents a significant challenge for achieving a favorable therapeutic window [8].

Other names

eIF-5AeIF-5A1eIF-4DRev-binding factor

Inhibition of the hypusination post-translational modification pathway, specifically targeting deoxyhypusine synthase (DHPS) or deoxyhypusine hydroxylase (DOHH), to prevent the activation of eIF5A1 and subsequent translation of polyproline-rich proteins.