eIF5A-dependent feedback inhibition from mRNA translation elongation to initiation induces apoptosis in tumour cells

Cancer progression is associated with disruption in protein synthesis, and novel therapies are being developed to target specific aspects of this process. Traditionally, these treatments have concentrated on the initiation phase of mRNA translation. However, recent discoveries indicate that issues in the elongation phase of translation, particularly alterations in eEF2 and eIF5A, also contribute to cancer cell growth. This research delves into the role of eIF5A, a crucial participant in this process, and its impact on mRNA translation elongation and initiation, as well as the subsequent changes in the nascent proteome. To investigate this, we utilize dynamic SILAC in conjunction with GC7 at both early and late treatment stages. By comprehending the state of translation after eIF5A inhibition, we can distinguish between direct and indirect protein targets of eIF5A. This understanding paves the way for more precise strategies in therapeutic efforts aimed at regulating mRNA translation and protein synthesis.