Eukaryotic translation initiation factor 5A (eIF5A) (eIF5A)

Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein and the only known cellular protein to undergo hypusination, a unique post-translational modification on Lysine 50 (K50). This modification, catalyzed by the enzymes deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), is essential for eIF5A's role in resolving ribosomal stalling at polyproline sequences during translation elongation and termination (nih.gov, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151112/). In various cancers, including multiple myeloma and B-cell lymphomas, eIF5A is frequently overexpressed and functions as a pro-survival factor, often regulated by the MYC oncogene (aacrjournals.org, https://aacrjournals.org/cancerres/article/77/1/109/614543/eIF5A-Hypusination-is-Essential-for-MYC-Driven). The K50R mutation (eIF5AK50R) prevents hypusination, rendering the protein non-functional and capable of inducing apoptosis (researchgate.net, https://www.researchgate.net/publication/351284444_Nanotechnology_for_the_delivery_of_precision_medicine). Therapeutic strategies such as SNS01-T utilize a dual approach by delivering an siRNA to silence endogenous eIF5A mRNA while simultaneously expressing the pro-apoptotic eIF5AK50R mutant via a plasmid or mRNA delivery system (kinampark.com, http://kinampark.com/Publications/2020-Piotrowski-Daspit-ADDR.pdf). Additionally, small-molecule inhibitors like GC7 target the hypusination pathway to suppress eIF5A activity in hyperproliferative and viral diseases (nih.gov, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312682/).

Other names

eIF-5AeIF-4DEIF5A1EIF5A2Rev-binding factor

siRNA-mediated knockdown of native eIF5A mRNA and simultaneous expression of the pro-apoptotic eIF5AK50R mutant; inhibition of deoxyhypusine synthase (DHPS) or deoxyhypusine hydroxylase (DOHH) to prevent eIF5A hypusination.