| 2001 |
EIF5A2 encodes a 153-amino-acid eIF5A isoform that, like eIF5A1, receives the unique spermidine-derived post-translational modification hypusine, which is necessary for eIF5A biochemical activity. The gene spans 17 kb with 5 exons and produces two mRNAs via differential polyadenylation sharing the same coding sequence. |
Molecular cloning, sequence characterization, gene structure analysis |
Genomics |
Medium |
11161802
|
| 2006 |
eIF5A-2 precursor protein is modified by hypusination comparably to eIF5A-1 in UACC-1598 cells. eIF5A-2 mRNA is inefficiently translated relative to eIF5A-1, with only a small fraction associating with polysomes; the elements causing inefficient translation reside outside the open reading frame (within the UTRs). Both isoforms are similarly stable once synthesized. |
Sucrose gradient polysome fractionation, mammalian expression vectors in 293T cells, Western blot, pulse-chase stability assay |
The FEBS journal |
Medium |
16519677
|
| 2004 |
EIF5A2 has tumorigenic activity: ectopic expression enables anchorage-independent growth in soft agar and tumor formation in nude mice. Antisense DNA against eIF5A2 inhibits cell growth in an ovarian cancer cell line (UACC-1598) that harbors EIF5A2 amplification as double minutes. |
Soft agar colony formation, nude mouse xenograft, antisense oligonucleotide knockdown, copy-number reduction |
Cancer research |
High |
15205331
|
| 2011 |
EIF5A2 overexpression promotes colorectal carcinoma cell motility, invasion, and epithelial-mesenchymal transition (EMT) in vitro and metastasis in vivo. Mechanistically, EIF5A2 upregulates MTA1 via enhanced enrichment of c-Myc on the MTA1 promoter; MTA1 knockdown eliminates EIF5A2-driven migration, invasion, and EMT. |
Ectopic overexpression and siRNA knockdown in CRC cell lines, in vitro invasion/migration assays, in vivo metastasis model, ChIP assay for c-Myc on MTA1 promoter, epistasis by MTA1 siRNA rescue |
Gut |
High |
21813470
|
| 2011 |
Transgenic overexpression of eIF5A2 in mice accelerates organismal aging (decreased growth, shortened lifespan, kyphosis, osteoporosis, impaired wound healing) by increasing chromosomal instability. Mechanistically, eIF5A2 represses p19 (ARF), thereby destabilizing p53 in mouse embryo fibroblasts, leading to accumulation of mitotic errors (misaligned/lagging chromosomes, anaphase bridges, micronuclei) and increased aneuploidy. |
eIF5A2 transgenic mouse model, MEF isolation, immunohistochemistry, Western blot (p19, p53), cytogenetic analysis of mitotic figures, flow cytometry for aneuploidy |
BMC cancer |
Medium |
21612665
|
| 2013 |
EIF5A2 is a downstream target of phosphorylated Akt (PI3K/Akt pathway) in melanoma cells. EIF5A2 overexpression increases, and knockdown decreases, melanoma cell invasion and MMP-2 activity. |
Tissue microarray, EIF5A2 overexpression/knockdown in melanoma cell lines, invasion assay, zymography for MMP-2 activity, correlation with Akt phosphorylation status |
British journal of cancer |
Medium |
24178756
|
| 2014 |
EIF5A2 activates TGF-β1 expression to induce EMT in bladder cancer cells. Specifically, EIF5A2 stabilizes STAT3 and stimulates its nuclear localization, resulting in increased STAT3 binding to the TGF-β1 promoter and enhanced TGF-β1 transcription. |
EIF5A2 overexpression and knockdown in bladder cancer cell lines, ChIP assay for STAT3 on TGF-β1 promoter, Western blot for STAT3 nuclear localization, EMT marker analysis, in vivo metastasis model |
British journal of cancer |
High |
24504366
|
| 2014 |
EIF5A2 ablation in hepatocellular carcinoma inhibits tumor angiogenesis by reducing MMP-2 expression. EIF5A2 silencing increases vessel wall continuity, blood perfusion, and tumor oxygenation. EIF5A2 enhances MMP-2 activity via activation of the p38 MAPK and JNK/c-Jun signaling pathways. |
EIF5A2 knockdown in HCC cell lines and xenografts, fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays, tumor hypoxia assays, Western blot for p38/JNK/c-Jun |
Oncotarget |
High |
25071013
|
| 2014 |
EIF5A2 is induced by hypoxia (4–8 fold) in esophageal squamous cell carcinoma cells, and there is bidirectional regulation between EIF5A2 and HIF1α (each upregulates the other). EIF5A2 promotes HIF1α expression and downstream VEGF, contributing to angiogenesis and EMT. |
Luciferase reporter assay, chromatin immunoprecipitation (HIF1α on EIF5A2 promoter), quantitative RT-PCR, EIF5A2 overexpression/knockdown, xenograft tumors with vessel counting |
Gastroenterology |
High |
24561231
|
| 2022 |
HERC3 E3 ubiquitin ligase directly interacts with EIF5A2 via its RCC1 domain, promotes K27- and K48-linked ubiquitination of EIF5A2 via its HECT domain, and targets EIF5A2 for proteasomal degradation. The ubiquitination sites on EIF5A2 were identified as K47, K67, K85, and K121. HERC3-mediated degradation of EIF5A2 inhibits EMT through the TGF-β/Smad2/3 pathway. |
Co-immunoprecipitation, GST pulldown, immunoprecipitation with ubiquitin linkage-specific antibodies, site-directed mutagenesis of EIF5A2 lysine residues, in vivo and in vitro ubiquitination assays |
Cell death & disease |
High |
35064108
|
| 2021 |
EIF5A2 promotes EMT in ovarian cancer cells via activation of the TGFβ pathway. CRISPR/Cas9 knockout of EIF5A2 inhibits EMT, cell migration, invasion, and ovarian tumor growth and metastasis in orthotopic mouse models, while EIF5A2 overexpression promotes these phenotypes. |
Lentiviral CRISPR/Cas9 nickase knockout, lentiviral overexpression, in vitro migration/invasion assays, orthotopic ovarian cancer mouse model, Western blot for TGFβ pathway and EMT markers |
Cell & bioscience |
High |
33827661
|
| 2021 |
EIF5A2 promotes stemness in ovarian cancer cells via the E2F1/KLF4 pathway. EIF5A2 knockdown reduces KLF4 expression through E2F1, and KLF4 overexpression can partially rescue stem-like properties abolished by EIF5A2 knockdown; the transcription factor E2F1 directly binds the KLF4 promoter. |
EIF5A2 knockdown (siRNA), RNA-seq, sphere-forming assays, western blot, flow cytometry, in vivo xenograft, E2F1 epistasis rescue experiments |
Stem cell research & therapy |
Medium |
33726845
|
| 2021 |
Androgen receptor (AR) positively regulates EIF5A2 expression in androgen-dependent prostate cancer cells in response to DHT stimulation; anti-androgen bicalutamide reduces EIF5A2 expression. EIF5A2 knockdown eliminates DHT-induced EMT and invasion/migration. |
DHT stimulation and bicalutamide treatment of AR-positive/negative PCa cell lines, EIF5A2 knockdown, Western blot for EMT markers, in vivo lung metastasis assay with luciferase imaging |
Cell death discovery |
Medium |
34864817
|
| 2021 |
The deubiquitinating enzyme ATXN3 directly binds EIF5A2 and stabilizes it by reducing its ubiquitination and proteasomal degradation; ATXN3 promotes EIF5A2-dependent proliferation and metastasis in anaplastic thyroid carcinoma cells. |
Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function experiments, Western blot for EIF5A2 stability |
Molecular and cellular endocrinology |
Medium |
34428509
|
| 2022 |
EIF5A2 interacts with AGR2 (anterior gradient 2) by co-immunoprecipitation in cervical cancer cells; AGR2 overexpression reverses the reduction in proliferation, migration, invasion, and cisplatin sensitivity caused by EIF5A2 knockdown, placing AGR2 downstream of EIF5A2. |
Co-immunoprecipitation, EIF5A2 knockdown, AGR2 overexpression epistasis rescue, proliferation/apoptosis/invasion assays |
Pharmacology |
Medium |
35640539
|
| 2023 |
EIF5A2 promotes doxorubicin resistance in bladder cancer cells through the TGF-β signaling pathway; EIF5A2 upregulates TGF-β1, p-Smad2, and p-Smad3, and a TGF-β pathway activator (SRI-011381) reverses the sensitizing effect of EIF5A2 knockdown. |
Doxorubicin-resistant cell line construction, EIF5A2 siRNA knockdown, TGF-β pathway activator rescue, Western blot for TGF-β1/p-Smad2/3, CCK-8 viability assay |
Discovery medicine |
Medium |
38058082
|
| 2023 |
EIF5A2 K50R knock-in mice (CRISPR-Cas9) preventing hypusination at lysine-50 confirm that hypusine formation is required for eIF5A2 activation; metabolomic analysis of primary mouse dermal fibroblasts from eif5a2-K50R/K50R mice reveals significant alterations in the metabolite landscape, including increased tryptophan, kynurenine, pyridoxine, NAD, riboflavin, FAD, pantothenate, and CoA levels compared to controls. |
CRISPR-Cas9 K50R knock-in mouse model, Western blot with anti-hypusine antibody, metabolomics of primary dermal fibroblasts |
Biology open |
High |
36848144
|
| 2024 |
TRIM71 (tripartite motif containing 71) directly interacts with eIF5A2 (verified by co-immunoprecipitation) and decreases eIF5A2 protein stability without affecting its mRNA level; TRIM71 overexpression inhibits LSCC tumor growth, and this anti-tumor effect is abolished by eIF5A2 overexpression. |
Co-immunoprecipitation, cycloheximide chase assay (protein half-life), quantitative PCR (mRNA level unchanged), overexpression epistasis rescue, in vivo xenograft |
Applied biochemistry and biotechnology |
Medium |
39579322
|
| 2025 |
EIF5A2 protein synthesis is regulated at the translational level by polyamines: miR-6514-5p binds the 5'-UTR of eIF5A2 mRNA and negatively regulates its translation; polyamines inhibit miR-6514-5p function, thereby facilitating eIF5A2 synthesis. Proteomic analysis shows eIF5A2 and eIF5A1 regulate distinct sets of proteins, and eIF5A2 (not eIF5A1) is important for cancer cell growth. eIF5A2 silencing differentially regulates specific ribosomal proteins (RPS27A, RPL36A, RPL22L1) associated with cancer malignancy. |
Polyamine treatment with miR-6514-5p analysis, 5'-UTR reporter assays, eIF5A1/eIF5A2-specific siRNA knockdown, quantitative proteomics, cell proliferation assays |
The Journal of biological chemistry |
High |
40617352
|
| 2026 |
eIF5A2-dependent translation elongation specifically regulates the synthesis of proteins with proline-rich motifs, including MTFR1 (mitochondrial fission regulator 1). A high-throughput screen identified orlistat and andrographolide as inhibitors of eIF5A2-dependent translation elongation. eIF5A2 silencing and these inhibitors suppress heparanase 1 (but not MMP-2 or MMP-9) expression and inhibit cancer cell invasion. |
MTFR1-luciferase reporter high-throughput screen (1744 compounds), eIF5A2 siRNA knockdown, invasion assays, Western blot for heparanase 1/MMP2/MMP9 |
Biological & pharmaceutical bulletin |
Medium |
41730614
|
| 2026 |
Loss of EIF5A2 activity—either through gene hypermethylation (epigenetic silencing) or pharmacological inhibition of its hypusine post-translational modification—induces venetoclax sensitivity in AML cells. |
Gene methylation analysis, pharmacological inhibition of hypusination, venetoclax sensitivity assays in AML cell lines |
British journal of haematology |
Medium |
41606290
|
| 2019 |
miR-9 enhances chemosensitivity to daunorubicin in AML cells by targeting EIF5A2; EIF5A2 knockdown reduces MCL-1 expression, and the sensitizing effect of miR-9 requires downregulation of EIF5A2, placing MCL-1 downstream of EIF5A2 in this context. |
miR-9 overexpression/knockdown, EIF5A2 siRNA, Western blot for MCL-1, cell viability and apoptosis assays, epistasis by EIF5A2 rescue of miR-9 effects |
International journal of biological sciences |
Medium |
30745844
|
| 2020 |
EIF5A2 controls EMT and chemoresistance in thyroid and other cancers via the TGF-β/Smad2/3 signaling pathway. In anaplastic thyroid carcinoma, EIF5A2 overexpression upregulates p-Smad2/3, and TGF-β pathway inhibition (SB431542 or Smad3 siRNA) blocks the growth-promoting effect of EIF5A2 overexpression. |
shRNA knockdown, ectopic overexpression, recombinant TGF-β1 rescue, SB431542 pharmacological inhibition, Smad3 siRNA, Western blot for p-Smad2/3, in vitro and xenograft experiments |
Oncology research |
Medium |
32138807
|
| 2022 |
EIF5A2 overexpression activates the PI3K/AKT/mTOR signaling pathway and upregulates Cyclin D1, Cyclin D3, MMP2, and MMP9 to promote intrahepatic cholangiocarcinoma cell proliferation, migration, and invasion. |
EIF5A2 overexpression/knockdown, Western blot for PI3K/AKT/mTOR components and cell cycle proteins, proliferation (CCK-8, EdU), invasion/migration (Transwell, scratch) assays |
Clinics and research in hepatology and gastroenterology |
Low |
35792239
|