{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved, unique protein that plays a central role in regulating mRNA translation and, consequently, diverse aspects of cellular homeostasis. Its function critically depends on a distinctive post‐translational modification—hypusination—wherein the polyamine spermidine is used by deoxyhypusine synthase and deoxyhypusine hydroxylase to modify a specific lysine residue, an essential event for its activity and proper cytoplasmic localization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " By facilitating both translation initiation and elongation—especially alleviating ribosome stalling at certain pausing motifs—eIF5A promotes efficient synthesis of proteins required for cell‐cycle progression, stress responses, and differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Two isoforms are expressed in mammals: the ubiquitously present eIF5A1, which is indispensable for normal cellular proliferation and embryonic development"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and the more tissue‐restricted eIF5A2 that is frequently upregulated in a variety of cancers and has been implicated as a potential oncogene."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": " Moreover, reversible acetylation of eIF5A (or specifically eIF5A2) further modulates its subcellular distribution and hints at regulatory roles beyond translation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its established functions in protein synthesis, eIF5A influences several key cellular processes. It regulates the translation of oncogenic proteins such as MYC and can engage in feed‐forward loops with KRAS signaling, thereby contributing to tumorigenic programs in cancers like pancreatic ductal adenocarcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " In addition, eIF5A is involved in the control of apoptosis by modulating p53 activity and the expression of Bcl-2 family members"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": ", and it plays a role in autophagy by ensuring efficient translation of autophagy-related proteins."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " These multifaceted functions position eIF5A as a molecular rheostat, coordinating protein synthesis with cell growth, stress responses, and metabolic reprogramming—a convergence that is significant both during normal embryonic development"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "and in the evolution of cancer phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Daniel J Puleston, Michael D Buck, Ramon I Klein Geltink, et al. 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