Eukaryotic translation initiation factor 5A-1 (eIF5A1) (eIF5A1)

Eukaryotic translation initiation factor 5A-1 (eIF5A1) is a small, ubiquitous protein that is essential for cell viability and is highly conserved across eukaryotes [1, 2]. It is unique for being the only protein known to undergo hypusination, a post-translational modification where a lysine residue is converted to hypusine by the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) [3]. This modification is strictly required for eIF5A to perform its primary function: facilitating the translation of mRNAs containing difficult-to-translate sequences, such as polyproline motifs [5]. Beyond translation elongation, eIF5A is involved in mRNA decay, nuclear export of specific RNAs, and cell cycle progression [1, 4]. In clinical contexts, eIF5A is frequently upregulated in various cancers, including pancreatic, lung, and colorectal cancers, where it promotes tumor growth and metastasis [4]. It also plays a critical role in viral replication, notably as a cofactor for the HIV-1 Rev protein [1]. Pharmacological targeting of eIF5A typically involves inhibiting the hypusination pathway, with small molecules like GC7 or iron chelators that disrupt DOHH activity [3, 4]. Because of its central role in protein synthesis, eIF5A represents a potent but challenging therapeutic target due to potential toxicity in normal tissues [4].

Other names

eIF-5AeIF-5A1eIF-4DRev-binding factorEIF5A

Inhibition of the hypusination post-translational modification pathway, specifically targeting the enzymes deoxyhypusine synthase (DHPS) or deoxyhypusine hydroxylase (DOHH), which prevents the activation of eIF5A and subsequently stalls the translation of polyproline-containing proteins involved in oncogenesis and viral replication [3, 4, 5].