| 1990 |
The ATE1 gene of S. cerevisiae encodes an arginyl-tRNA-protein transferase (R-transferase) that catalyzes post-translational conjugation of Arg to the N-termini of acceptor proteins; expression in E. coli confirmed this catalytic activity, and null ate1 mutants lack Arg-transferase activity and cannot degrade N-end rule substrates requiring Nt-arginylation. |
Heterologous expression in E. coli (functional complementation), null mutant analysis with enzymatic assay and protein degradation readout |
The Journal of biological chemistry |
High |
2185248
|
| 2014 |
ATE1 can arginylate internal side-chain carboxylates (Asp and Glu residues) within intact proteins in vivo, in addition to N-terminal alpha-amino groups, demonstrating an unconventional midchain arginylation mechanism. |
Mass spectrometry-based proteomics (MS/MS), in vitro arginylation assay with purified ATE1 |
Chemistry & biology |
Medium |
24529990
|
| 2022 |
Crystal structure of Kluyveromyces lactis Ate1 reveals a 58-kDa two-domain R-transferase where both domains together recognize the acidic N-terminal residue of the acceptor substrate and the Arg-tRNAArg cosubstrate (including its 3'-proximal tRNA segment), with the active site located between the two domains; hemin (Fe3+-heme) inhibits Nt-arginylation and induces disulfide-mediated oligomerization of Ate1. |
X-ray crystallography, in vitro and in vivo arginylation assays, site-directed mutagenesis guided by structural data |
Proceedings of the National Academy of Sciences of the United States of America |
High |
35878037
|
| 2022 |
Crystal structure of S. cerevisiae ATE1 in the apo form reveals a bilobed protein with a GCN5-related N-acetyltransferase (GNAT) fold; structural and electrostatic analyses identify the domain-domain interface as the catalytic site and tRNA-binding region; the N-terminal domain that binds a regulatory [Fe-S] cluster is dynamic and disordered when metal-free. |
X-ray crystallography, SEC-SAXS, cryo-EM 2D class averaging, structural superposition |
Journal of molecular biology |
High |
36087779
|
| 2025 |
Cryo-EM structure of human ATE1 in complex with Arg-tRNAArg and an Nt-Asp peptide reveals two adjacent binding pockets for the substrate and the tRNA cosubstrate, the tRNA being wrapped by a long unstructured loop; in the apo state ATE1 forms a homodimer; substrate selectivity is achieved through multivalent interactions with Kd values in the micromolar range. |
Cryo-EM structure determination, biochemical binding assays |
Autophagy |
High |
40099869
|
| 2024 |
Mouse ATE1 contains an intrinsically disordered region (IDR) absent in yeast ATE1; computational and HDX-MS analyses suggest this IDR facilitates complex formation between ATE1 and tRNAArg, adding regulatory complexity not present in the yeast enzyme. |
SEC, SAXS, hydrogen-deuterium exchange mass spectrometry (HDX-MS), AlphaFold modeling |
Biochemistry |
Medium |
39642180
|
| 2023 |
ATE1 binds a regulatory iron-sulfur ([Fe-S]) cluster in its N-terminal domain; the cluster is oxygen-sensitive and functions as an oxygen sensor to regulate ATE1 activity, as it decomposes upon purification in the presence of O2. |
Anaerobic chemical reconstitution of [Fe-S] cluster in purified ScATE1 and MmATE1, metal analysis |
Methods in molecular biology |
Medium |
37010764
|
| 2013 |
ATE1 co-immunoprecipitates with myosin II from platelet lysates; platelet-specific ATE1 knockout mice show enhanced myosin regulatory light chain phosphorylation at Ser19 (activating myosin), enhanced clot retraction, and enhanced in vivo thrombus formation, placing ATE1-mediated arginylation upstream of myosin II contractility regulation. |
Conditional knockout mouse model, co-immunoprecipitation, phosphorylation analysis, clot retraction assay, in vivo thrombosis assay |
Haematologica |
High |
24293517
|
| 2017 |
ATE1 localizes prominently to neuronal growth cones in addition to cell bodies; Ate1 mRNA contains zipcode-binding sequences that target it to growth cone tips where local translation occurs, co-localizing with arginylated β-actin; Ate1 conditional knockout in the nervous system reduces neurite outgrowth and F-actin levels in growth cones, and decreases doublecortin levels. |
Conditional knockout mouse (Nestin-Cre), fluorescence in situ hybridization (FISH), live-cell imaging, immunofluorescence, protein synthesis inhibitor treatment |
Developmental biology |
High |
28844905
|
| 2018 |
In Dictyostelium discoideum, Ate1 knockout eliminates focal actin adhesion sites at the substrate-attached surface, reduces adhesion, and alters chemotaxis; GFP-Ate1 rapidly relocates to newly forming actin-rich protrusions; mass spectrometry identified four arginylation sites in the major actin isoform plus sites on actin-binding proteins; actin purified from ate1-null cells shows diminished in vitro polymerization. |
Gene knockout, live-cell microscopy, mass spectrometry, in vitro actin polymerization assay, GFP-tagging/live imaging |
Molecular biology of the cell |
High |
30586322
|
| 2021 |
ATE1 facilitates proteasomal degradation of RGS7 in mouse embryonic fibroblasts; conditional Ate1 knockout in the nervous system elevates RGS7 protein levels in retinal ON-bipolar cells, leading to increased light-evoked response sensitivities; RGS7 degradation is abolished in Ate1 KO MEFs but is rapid via the proteasome in wildtype cells. |
Conditional nervous system knockout mouse, electroretinography, MEF cell-based proteasome inhibitor experiments, immunoblotting |
Scientific reports |
High |
33931669
|
| 2021 |
ATE1 inhibits liver cancer progression by regulating turnover of RGS5, which in turn suppresses Wnt/β-catenin signaling by affecting GSK3-β activity; loss- and gain-of-function assays confirmed RGS5 as a key effector downstream of ATE1. |
Lentivirus-mediated knockdown/overexpression, loss- and gain-of-function assays, GSK inhibitor treatment, in vitro and in vivo tumor models |
Molecular cancer research |
Medium |
34158395
|
| 2016 |
ATE1 promotes cell death and growth arrest in response to oxidative, heat, osmotic stress, heavy metals, and radiation; ATE1 protein levels and arginylation activity increase in wild-type cells under acute stress; ATE1-induced cell death requires its arginylation activity; ATE1 is required to suppress mutation frequency under DNA-damaging conditions in yeast and mammalian cells. |
Gene deletion/knockdown in yeast, mouse, and human cells; stress viability assays; enzymatic activity assays; mutation frequency assays under UV irradiation |
Cell death & disease |
Medium |
27685622
|
| 2024 |
Mitochondrial translocation of Ate1 is promoted by oxidative stress and is essential for inducing apoptotic cell death; Ate1-induced cell death depends on formation of the mitochondrial permeability transition pore and at least partly on the apoptosis-inducing factor; cytosolic protein degradation pathways (ubiquitin-proteasome, autophagy, ER stress) have negligible impact on Ate1-induced cell death. |
Budding yeast model, mitochondrial fractionation, genetic epistasis with permeability pore mutants and AIF deletion, live-cell imaging |
bioRxivpreprint |
Medium |
bio_10.1101_2024.11.22.624728
|
| 2020 |
The Ligand of Ate1 (Liat1) physically interacts with Ate1 and undergoes liquid-liquid phase separation in the nucleolus via an intrinsically disordered N-terminal region; Jumonji Domain Containing 6 (Jmjd6) hydroxylates Liat1 at its poly-K region, inhibiting nucleolar targeting of Liat1. |
Bimolecular fluorescence complementation, immunocytochemistry, phase separation assays, Jmjd6 enzymatic modification assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
33443146
|
| 2021 |
The mammalian Ate1 gene undergoes alternative splicing controlled by mutually exclusive exons 7a/7b; five conserved intronic RNA structural elements (R1-R5) regulate this splicing via competing base-pair interactions (R1/R3 vs R4/R3) and an ultra-long-range R2/R5 RNA structure (~30 kb); disrupting these interactions by mutation or LNA/DNA mixmers abolishes MXE splicing; exon 7a inclusion responds to RNA Pol II slowdown in a manner dependent on the R2/R5 interaction, indicating co-transcriptional regulation. |
Minigene mutagenesis (single, double, compensatory triple mutations), LNA/DNA mixmer blocking in endogenous pre-mRNA, RNA Pol II slowdown experiments |
Nucleic acids research |
High |
33330934
|
| 2021 |
Targeted proteomics found no evidence of Nt-arginylated β-actin (RDDI-) in wildtype cells or NAA80-knockout cells; only a very minor level of Nt-arginylation of cleaved β-actin (DDDI-) was detectable in NAA80-lacking cells but not in wildtype; the final maturation state of β-actin is Nt-acetylation by NAA80, not arginylation by ATE1 under normal conditions. |
State-of-the-art targeted proteomics/mass spectrometry in wildtype and NAA80-KO cells |
Journal of molecular biology |
Medium |
34896361
|
| 2024 |
In vitro, human tRNAArg directly binds the RNA recognition motifs (RRMs) of TDP-43, and the same TDP-43 constructs also bind native fungal tRNAPhe; mouse LIAT1 (Ligand of Ate1) binds human tRNAArg in vitro, identifying LIAT1 as an RNA-binding protein relevant to the arginylation machinery. |
In vitro binding assays with recombinant proteins and in vitro-transcribed tRNA |
microPublication biology |
Low |
39081859
|
| 2025 |
Using isotopic arginine labeling in an ex vivo ATE1 assay on biological lysates, 235 unique arginylation sites were identified in human proteomes, including both N-terminal and midchain sites; representative sites were validated for biological function. |
Isotopic arginine labeling, ex vivo ATE1 enzymatic assay, mass spectrometry (bottom-up proteomics) |
Nature chemical biology |
Medium |
40855110
|
| 2022 |
ATE1 depletion in melanoma cells reduces viability, migration, and colony formation; AXIN1 is identified as a putative arginylation substrate of ATE1 in melanoma, suggesting ATE1 may regulate AXIN1 function. |
siRNA/shRNA knockdown, cell viability and migration assays, substrate identification |
FEBS letters |
Low |
35561126
|
| 2025 |
ATE1 stabilizes MYC protein in breast cancer cells via ERK-mediated phosphorylation at Ser62; ATE1 depletion impairs MAPK-MYC-CDK6 axis activity, reduces cell cycle progression, and promotes apoptosis; rescue experiments confirmed that ATE1's tumor-promoting activity requires its arginyltransferase catalytic function. |
siRNA/shRNA knockdown, quantitative proteomics, R-catcher-based N-terminomics, flow cytometry, immunoblotting, xenograft mouse model |
Cell communication and signaling |
Medium |
40898325
|
| 2024 |
ATE1 mediates arginylation of the Newcastle disease virus haemagglutinin-neuraminidase (HN) protein at its N-terminus; addition of Arg amplifies arginylation of HN, reducing its stability and promoting ubiquitin-mediated proteasomal degradation; ATE1 knockdown and inhibition of ATE1 activity increase HN protein levels. |
ATE1 knockdown, enzymatic activity inhibition, Arg supplementation, ubiquitination assay, immunoblotting |
The Journal of general virology |
Medium |
39207120
|