Affinage

ASS1

Argininosuccinate synthase · UniProt P00966

Length
412 aa
Mass
46.5 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASS1 is the rate-limiting urea cycle enzyme that condenses citrulline and aspartate to form argininosuccinate, functioning as a central metabolic node linking nitrogen disposal, nucleotide biosynthesis, redox homeostasis, and chromatin regulation. In the cytosol, ASS1 controls aspartate availability for pyrimidine synthesis via CAD and mTOR/S6K1, promotes PHGDH degradation to restrain serine biosynthesis, and channels glutamine into reductive carboxylation to generate monounsaturated fatty acids through the mTORC1–SREBP1–SCD5 axis, conferring ferroptosis resistance (PMID:26560030, PMID:38710705, PMID:36892426). In the nucleus, ASS1 and ASL cooperate to produce fumarate that succinates SMARCC1, destabilizing the SWI/SNF chromatin-remodeling complex and attenuating p53-dependent cell-cycle gene transcription during the DNA damage response (PMID:38858597). ASS1 activity is circadianly regulated by CLOCK-mediated acetylation at K165/K176, transcriptionally controlled by opposing actions of HIF-1α (repressor) and c-MYC (activator), and subject to TRAF2-mediated ubiquitin-dependent degradation (PMID:28985504, PMID:27765932, PMID:34184805).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1979 High

    Establishing the chromosomal home of ASS1 at 9q34 provided the first physical framework for genetic studies of citrullinemia.

    Evidence Somatic cell hybrid panel with balanced reciprocal translocations involving chromosome 9

    PMID:219990

    Open questions at the time
    • Gene structure and regulatory elements not yet defined
    • No functional characterization at this stage
  2. 2011 Medium

    The unexpected finding that recombinant ASS1 directly binds LPS and suppresses endotoxemia in vivo suggested a moonlighting innate-immune function beyond ureagenesis.

    Evidence Gel-shift LPS-binding assay, macrophage cytotoxicity assay, rodent endotoxemia survival model

    PMID:21681813

    Open questions at the time
    • Mechanism of ASS1 secretion not established
    • No structural basis for LPS binding
    • Not independently replicated
  3. 2014 High

    Demonstrating that arginine starvation kills ASS1-deficient breast cancer cells via mitochondrial oxidative stress and autophagy-dependent death established the therapeutic rationale for ADI-PEG20 in ASS1-low tumors.

    Evidence ADI-PEG20 treatment, autophagy knockdown, mitochondrial function assays, in vivo xenografts

    PMID:24692592

    Open questions at the time
    • Precise mitochondrial target of oxidative stress unknown
    • Biomarker for autophagy competence not defined
  4. 2015 High

    Linking ASS1 deficiency to de novo pyrimidine synthesis via aspartate accumulation and mTOR/S6K1-dependent CAD activation revealed a non-urea-cycle metabolic function explaining the proliferative advantage of ASS1-silenced cancers.

    Evidence Metabolic tracing, siRNA, mTOR/S6K1 inhibition, citrullinemia patient samples

    PMID:26560030

    Open questions at the time
    • Whether CAD activation is the dominant growth-promoting mechanism or one of several parallel pathways
    • Contribution of other aspartate-consuming reactions not dissected
  5. 2017 High

    Multiple studies converged to define a layered regulatory architecture: CLOCK acetylates ASS1 at K165/K176 to inactivate it circadianly, while HIF-1α and c-MYC antagonistically govern ASS1 transcription, and arginine starvation derepresses the promoter through chromatin remodeling involving HDAC2/Sin3A and PHD2-mediated HIF-1α degradation.

    Evidence In vitro acetylation, site-directed mutagenesis, ChIP, promoter reporters, siRNA (multiple labs)

    PMID:27765932 PMID:28883660 PMID:28985504

    Open questions at the time
    • Relative contribution of acetylation vs. transcriptional regulation to in vivo ASS1 flux not quantified
    • Deacetylase that reverses CLOCK acetylation not identified
  6. 2017 Medium

    PRMT7 was identified as a direct ASS1-binding partner, and citrullinemia-causing mutations disrupt this interaction, raising the possibility of a regulatory or chaperone role for PRMT7 in ASS1 function.

    Evidence Yeast two-hybrid, pulldown, site-directed mutagenesis

    PMID:28587924

    Open questions at the time
    • Functional consequence of ASS1–PRMT7 interaction on enzymatic activity not determined
    • Whether PRMT7 methylates ASS1 not tested
    • Not independently replicated
  7. 2017 High

    Arginine deprivation rewires central carbon metabolism in ASS1-deficient cells—reducing PKM2 and the Warburg effect while increasing serine biosynthesis—revealing synthetic lethality with glutaminase inhibition.

    Evidence Metabolite profiling, in vivo xenograft regression with combined arginine deprivation and glutaminase inhibitor

    PMID:28122247

    Open questions at the time
    • Clinical translation of combination therapy not yet validated
    • Metabolic heterogeneity across tumor types not addressed
  8. 2020 High

    Under glucose deprivation, c-MYC-induced ASS1 feeds NO synthesis, and NO S-nitrosylates gluconeogenic enzymes PC and PCK to activate serine/glycine/purine biosynthesis—uncovering a direct link between arginine metabolism and one-carbon metabolism.

    Evidence c-MYC ChIP, metabolic tracing, S-nitrosylation assays, in vivo mouse models

    PMID:35121952

    Open questions at the time
    • Identity and specificity of the S-nitrosylation sites on PC/PCK not fully characterized
    • Whether this pathway operates outside cancer contexts unknown
  9. 2021 High

    Two complementary studies showed ASS1 suppresses tumorigenesis by (a) directly binding PHGDH to promote its ubiquitin-dependent degradation, restricting serine synthesis, and (b) cooperating with ASL to redirect aspartate away from pyrimidines and generate NO—establishing that both enzymatic and non-enzymatic ASS1 functions restrain cancer growth.

    Evidence Reciprocal Co-IP, ubiquitination assays, enzyme-dead mutants, metabolomics, in vivo xenografts

    PMID:34861885 PMID:38710705

    Open questions at the time
    • E3 ligase responsible for PHGDH ubiquitination downstream of ASS1 not identified
    • Relative contribution of NO vs. aspartate sequestration to tumor suppression unclear
  10. 2021 Medium

    The lncRNA LOC113230 was shown to scaffold LRPPRC and TRAF2 E3 ligase onto ASS1, promoting its ubiquitination and degradation; Snail-mediated repression of this lncRNA stabilizes ASS1 to support colorectal cancer migration.

    Evidence RIP, Co-IP, ubiquitination assay, xenograft experiments

    PMID:34184805

    Open questions at the time
    • Ubiquitination sites on ASS1 targeted by TRAF2 not mapped
    • Generalizability beyond colorectal cancer not tested
  11. 2023 High

    ASS1 was found to redirect glutamine into reductive carboxylation and activate the mTORC1–SREBP1–SCD5 lipogenesis axis, conferring ferroptosis resistance by reducing lipid ROS—broadening ASS1's metabolic reach to lipid homeostasis.

    Evidence Stable isotope-labeled glutamine tracing, transcriptomics, genetic knockout, in vivo ferroptosis assays

    PMID:36892426

    Open questions at the time
    • Molecular mechanism connecting ASS1 enzymatic products to reductive carboxylation not defined
    • Whether ferroptosis resistance depends on mTORC1 or SCD5 independently not resolved
  12. 2024 High

    A nuclear role for ASS1 was established: DNA damage induces ASS1 nuclear translocation where, together with ASL, it generates fumarate that succinates SMARCC1, destabilizing the SWI/SNF complex and dampening p53-target transcription—revealing a chromatin-regulatory moonlighting function.

    Evidence Subcellular fractionation, succination assays, Co-IP, ChIP, genetic manipulation

    PMID:38858597

    Open questions at the time
    • Nuclear import mechanism for ASS1 not identified
    • Full spectrum of succinated chromatin targets unknown
    • Whether nuclear ASS1 operates in non-cancer cells not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the mechanism of ASS1 nuclear import, whether PRMT7 methylates ASS1, the structural basis for ASS1's non-enzymatic interactions (PHGDH, LPS), and how tissue-specific regulatory inputs are integrated to control ASS1 flux in vivo.
  • Nuclear import signal or transport mechanism not characterized
  • No crystal structure of ASS1 with any binding partner besides substrates
  • In vivo contribution of individual post-translational modifications to ASS1 flux not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-1640170 Cell Cycle 1 R-HSA-4839726 Chromatin organization 1 R-HSA-73894 DNA Repair 1 R-HSA-9909396 Circadian clock 1
Partners
ASLBMAL1CLOCKMANFPHGDHPRMT7SMARCC1TRAF2

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 ASS1 deficiency in cancer increases cytosolic aspartate levels, which activates CAD (carbamoyl-phosphate synthase 2, aspartate transcarbamylase, and dihydroorotase complex) by upregulating substrate availability and increasing CAD phosphorylation by S6K1 through the mTOR pathway, thereby fostering de novo pyrimidine synthesis and supporting cancer cell proliferation. Metabolic tracing, siRNA knockdown, pharmacological inhibition of mTOR/S6K1, comparison of citrullinemia type I vs. type II patient samples Nature High 26560030
2017 CLOCK directly acetylates ASS1 at K165 and K176 (facilitated by BMAL1) to inactivate ASS1 enzymatic activity, creating circadian oscillation of ASS1 acetylation in human cells and mouse liver, and thereby driving circadian regulation of ureagenesis. In vitro acetylation assay, site-directed mutagenesis of acetylation sites, Co-IP of CLOCK-ASS1 interaction, mass spectrometry identification of acetylation sites Molecular cell High 28985504
2017 ASS1 expression is regulated by HIF-1α (negative regulator) and c-Myc (positive regulator) through reciprocal binding to the ASS1 promoter; the clock protein DEC1 acts as master regulator of HIF-1α and c-Myc that control ASS1 transcription. Cisplatin suppresses ASS1 via upregulation of HIF-1α and downregulation of c-Myc. ChIP assay, promoter reporter assays, siRNA knockdown, overexpression experiments, western blotting Oncotarget Medium 27765932
2017 Arginine starvation induces ASS1 promoter derepression via a chromatin remodeling mechanism: p300 dissociates from the ASS1 promoter, allowing HDAC2/Sin3A to deacetylate H3K14ac and H3K27ac, which facilitates PHD2-driven proteasomal degradation of HIF-1α in situ at the ASS1 promoter. ChIP assay, Co-IP, siRNA knockdown, histone modification analysis, proteasome inhibitor experiments Scientific reports Medium 28883660
2018 Under hypoxia, HIF-1α induces miR-224-5p which further downregulates ASS1 expression; ASS1-depleted cancer cells maintain higher intracellular pH and depend less on extracellular glutamine, providing a redox and pH advantage under acidic conditions. siRNA knockdown, miRNA overexpression, intracellular pH measurement, metabolite assays, HIF-1α manipulation Cancer research Medium 30573518
2014 Prolonged arginine starvation (via ADI-PEG20) in ASS1-deficient breast cancer cells induces mitochondrial oxidative stress, impairs mitochondrial bioenergetics and integrity, and causes autophagy-dependent cell death; this cytotoxicity requires autophagy competence. ADI-PEG20 treatment, autophagy knockdown/inhibition, mitochondrial function assays, in vivo xenograft models Science signaling High 24692592
2017 Arginine deprivation in ASS1-deficient cancers inhibits the Warburg effect by reducing PKM2 expression and phosphorylation, and upregulates PHGDH to increase serine biosynthesis and glutamine anaplerosis; concurrent arginine deprivation and glutaminase inhibition is synthetic lethal. Metabolite profiling, western blotting, in vivo xenograft tumor regression, pharmacological inhibition Cell reports High 28122247
2020 Under glucose deprivation, ASS1 expression is induced by c-MYC, and high ASS1 expression increases nitric oxide synthesis and activates gluconeogenic enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase via S-nitrosylation, enhancing flux through gluconeogenesis and subsequently serine, glycine, and purine synthesis. c-MYC ChIP, metabolic tracing, S-nitrosylation assays, enzyme activity assays, in vivo mouse models Nature cancer High 35121952
2023 ASS1 promotes reductive carboxylation of cytosolic glutamine and compromises oxidative TCA cycle glutamine anaplerosis, reducing mitochondrial-derived lipid reactive oxygen species; additionally, ASS1 activates the mTORC1-SREBP1-SCD5 axis to promote de novo monounsaturated fatty acid synthesis using acetyl-CoA from the glutamine reductive pathway, thereby conferring ferroptosis resistance. Stable isotope-labeled glutamine metabolomics, transcriptome sequencing, genetic knockdown/knockout, in vitro and in vivo ferroptosis assays Cancer research High 36892426
2024 Following acute DNA damage induction, ASS1 expression is elevated in both the cytosol and nucleus with partial p53 dependency; in the cytosol, ASS1 restricts nucleotide synthesis to restrain cell cycle progression; in the nucleus, ASS1 and ASL generate fumarate for succination of SMARCC1, destabilizing the SMARCC1-SNF5 chromatin-remodeling complex and decreasing transcription of a subset of p53-regulated cell cycle genes. Subcellular fractionation, metabolomics, succination assays, Co-IP, ChIP, genetic manipulation of ASS1 and ASL Nature metabolism High 38858597
2021 ASS1 directly binds to PHGDH (phosphoglycerate dehydrogenase) and promotes its ubiquitination-mediated degradation to inhibit serine synthesis, thereby suppressing tumorigenesis in triple-negative breast cancer. Co-IP, ubiquitination assay, genetic knockdown/overexpression, PHGDH knockout rescue experiments, proliferation assays Cell death & disease High 38710705
2021 Snail promotes colorectal cancer migration by preventing LOC113230 (a Snail-repressed lncRNA)-mediated degradation of ASS1; LOC113230 acts as a scaffold recruiting LRPPRC and the TRAF2 E3 ubiquitin ligase to ASS1, causing enhanced ubiquitination and degradation of ASS1, thereby decreasing arginine synthesis. RIP assay, Co-IP, ubiquitination assay, siRNA knockdown, xenograft experiments EMBO reports Medium 34184805
2019 Androgen receptor decreases ASS1 expression in renal cell carcinoma via ASS1P3 (a pseudogene of ASS1), which acts as a competing endogenous RNA (ceRNA) to sponge miR-34a-5p; miR-34a-5p binds the 3'UTR of ASS1 mRNA to suppress ASS1 protein expression. RIP assay, AGO2 assay, 3'UTR luciferase reporter, siRNA knockdown, overexpression, preclinical in vivo models Cell death & disease Medium 31000693
2022 PGAM1 negatively regulates ASS1 expression through the cAMP/AMPK/CEBPB signaling axis in breast cancer cells. RNA sequencing, siRNA knockdown, pharmacological manipulation of cAMP/AMPK pathway, western blotting, in vivo tumor models Molecular oncology Medium 35674458
2024 ASS1 enhances fatty acid oxidation (FAO) through AMPK/CPT1A axis to confer anoikis resistance in ovarian cancer; ASS1 overexpression disrupts the AMP/ATP balance to activate AMPK and downstream CPT1A, increasing FAO and ATP generation; CPT1A inhibition reverses ASS1-induced FAO. Genetic knockdown/overexpression, FAO assays, AMPK/CPT1A activity measurements, 3D culture anoikis assays Cancer letters Medium 38914306
2017 PRMT7 directly interacts with ASS1 (confirmed by yeast two-hybrid and pulldown assays); citrullinemia type I-associated mutations in ASS1 disrupt the ASS1-PRMT7 interaction. Yeast two-hybrid screening, pulldown assay, site-directed mutagenesis, computational interface mapping Journal of molecular biology Medium 28587924
2022 FXR (Farnesoid X receptor) directly promotes ASS1 transcription; FXR activation by its agonist obeticholic acid upregulates ASS1 expression, enhancing arginine synthesis and protecting against liver injury; ASS1-mediated arginine synthesis decreases hepatocyte apoptosis by reducing cytochrome C, PARP, and Caspase 3 levels. FXR agonist treatment, single-cell RNA-seq analysis, gene expression assays, apoptosis assays, in vivo liver injury model Biochemical and biophysical research communications Medium 35477090
2022 MANF (mesencephalic astrocyte-derived neurotrophic factor) physically interacts with ASS1 in the same immunoprecipitated complex; MANF knockout reduces ASS1 activity while MANF overexpression enhances ASS1 activity in vitro; ASS1 activates AMPK by generating intracellular AMP through the urea cycle. Immunoprecipitation-coupled MS proteomics, genetic knockout/overexpression, enzymatic activity assay, urea cycle metabolite profiling Acta pharmacologica Sinica Medium 35655095
2011 Recombinant ASS1 physically binds to LPS (shown by gel shift assay), suppresses E. coli growth in culture, reduces LPS cytotoxicity and TNF-α production in macrophages, and increases survival in rodent endotoxemia models, demonstrating a role for secreted ASS1 in innate immune responses to bacterial infection. Gel shift assay for LPS binding, bacterial growth assay, macrophage cytotoxicity assay, in vivo rodent endotoxemia model International immunopharmacology Medium 21481813
2021 ASS1 and ASL enzymatic activities together suppress ccRCC growth by redirecting aspartate away from pyrimidine synthesis, regulating nitric oxide (NO) generation, and limiting pyrimidine production; growth suppression requires intact enzymatic activity of both enzymes. Genetic re-expression of ASS1+ASL, enzyme-dead mutant constructs, metabolomics, 2D/3D growth assays, in vivo xenograft models Cancer & metabolism Medium 34861885
2024 β-sitosterol selectively targets ASS1 in ovarian cancer; inhibiting ASS1 enhances the interaction between Nrf2 and Keap1, causing ubiquitin-dependent degradation of Nrf2, which reduces transcription of antioxidant genes HO-1 and NQO1, leading to ROS accumulation that upregulates PTEN and suppresses AKT phosphorylation. Network pharmacology target prediction, in vitro binding assay, ubiquitination assay, genetic knockdown/overexpression, ROS measurement, in vivo mouse models Free radical biology & medicine Medium 38364944
1979 The ASS1 gene locus was chromosomally mapped to the distal portion of the long arm of human chromosome 9, in the region 9q34 to 9qter, by somatic cell hybrid analysis using cells with balanced reciprocal translocations. Somatic cell hybrid panel with human cells carrying balanced reciprocal translocations involving chromosome 9 regions Cytogenetics and cell genetics High 219990

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. Nature 306 26560030
2013 The polyphenol oleuropein aglycone protects TgCRND8 mice against Aß plaque pathology. PloS one 185 23951225
2022 Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology. Nature communications 167 35013236
2014 Arginine starvation impairs mitochondrial respiratory function in ASS1-deficient breast cancer cells. Science signaling 167 24692592
1991 Antibodies to proliferating cell nuclear antigen as S-phase probes in flow cytometric cell cycle analysis. Cancer research 159 1678682
2017 Arginine Deprivation Inhibits the Warburg Effect and Upregulates Glutamine Anaplerosis and Serine Biosynthesis in ASS1-Deficient Cancers. Cell reports 129 28122247
1999 Neogenesis vs. apoptosis As main components of pancreatic beta cell ass changes in glucose-infused normal and mildly diabetic adult rats. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 110 10385610
2018 The interactions of p53 with tau and Aß as potential therapeutic targets for Alzheimer's disease. Progress in neurobiology 81 29733887
2016 A metabolic synthetic lethal strategy with arginine deprivation and chloroquine leads to cell death in ASS1-deficient sarcomas. Cell death & disease 77 27735949
2009 Mutations and polymorphisms in the human argininosuccinate synthetase (ASS1) gene. Human mutation 75 19006241
2020 Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors. Nature cancer 73 35121952
2017 mTOR in Down syndrome: Role in Aß and tau neuropathology and transition to Alzheimer disease-like dementia. Free radical biology & medicine 71 28807816
1992 Use of ass' milk in multiple food allergy. Journal of pediatric gastroenterology and nutrition 71 1593372
2008 Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiology of aging 70 18771817
2017 Argininosuccinate synthase 1 (ASS1): A marker of unclassified hepatocellular adenoma and high bleeding risk. Hepatology (Baltimore, Md.) 68 28646562
2018 Exercise training as S-Klotho protein stimulator in sedentary healthy adults: Rationale, design, and methodology. Contemporary clinical trials communications 63 30023455
1998 Carbocyclic adenosine analogues as S-adenosylhomocysteine hydrolase inhibitors and antiviral agents: recent advances. Nucleosides & nucleotides 63 9708366
1979 Regional asssignments of the loci AK3, ACONS, and ASS on human chromosome 9. Cytogenetics and cell genetics 62 219990
2017 CLOCK Acetylates ASS1 to Drive Circadian Rhythm of Ureagenesis. Molecular cell 61 28985504
2015 Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies. Acta neuropathologica 61 26715565
2010 Ancient DNA from Nubian and Somali wild ass provides insights into donkey ancestry and domestication. Proceedings. Biological sciences 60 20667880
2023 ASS1-Mediated Reductive Carboxylation of Cytosolic Glutamine Confers Ferroptosis Resistance in Cancer Cells. Cancer research 55 36892426
2021 Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model. Journal of photochemistry and photobiology. B, Biology 55 33610085
2019 Arginine Starvation and Docetaxel Induce c-Myc-Driven hENT1 Surface Expression to Overcome Gemcitabine Resistance in ASS1-Negative Tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 54 31113844
2017 Transcription Factor AsMYC2 Controls the Jasmonate-Responsive Expression of ASS1 Regulating Sesquiterpene Biosynthesis in Aquilaria sinensis (Lour.) Gilg. Plant & cell physiology 51 29016977
2017 Serpentine endophytic bacterium Pseudomonas azotoformans ASS1 accelerates phytoremediation of soil metals under drought stress. Chemosphere 49 28686889
2007 Ass's milk in children with atopic dermatitis and cow's milk allergy: crossover comparison with goat's milk. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 48 18001430
2018 Acid-Induced Downregulation of ASS1 Contributes to the Maintenance of Intracellular pH in Cancer. Cancer research 45 30573518
2017 Mutations in the Human Argininosuccinate Synthetase (ASS1) Gene, Impact on Patients, Common Changes, and Structural Considerations. Human mutation 42 28111830
2016 Cisplatin-induced synthetic lethality to arginine-starvation therapy by transcriptional suppression of ASS1 is regulated by DEC1, HIF-1α, and c-Myc transcription network and is independent of ASS1 promoter DNA methylation. Oncotarget 42 27765932
2021 Non-productive angiogenesis disassembles Aß plaque-associated blood vessels. Nature communications 41 34035282
2013 Oxysterols decrease apical-to-basolateral transport of Aß peptides via an ABCB1-mediated process in an in vitro Blood-brain barrier model constituted of bovine brain capillary endothelial cells. Brain research 40 23603412
2014 Longitudinal testing of hippocampal plasticity reveals the onset and maintenance of endogenous human Aß-induced synaptic dysfunction in individual freely behaving pre-plaque transgenic rats: rapid reversal by anti-Aß agents. Acta neuropathologica communications 37 25540024
1995 Identification of a major hepatic copper binding protein as S-adenosylhomocysteine hydrolase. The Journal of biological chemistry 37 7657650
2021 Therapeutic targeting of argininosuccinate synthase 1 (ASS1)-deficient pulmonary fibrosis. Molecular therapy : the journal of the American Society of Gene Therapy 35 33508432
2016 Argininosuccinate synthetase 1 (ASS1) is a common metabolic marker of chemosensitivity for targeted arginine- and glutamine-starvation therapy. Cancer letters 34 27913198
2005 Synthesis, cytotoxicity, cellular uptake and influence on eicosanoid metabolism of cobalt-alkyne modified fructoses in comparison to auranofin and the cytotoxic COX inhibitor Co-ASS. Organic & biomolecular chemistry 33 16010362
2019 Androgen receptor regulates ASS1P3/miR-34a-5p/ASS1 signaling to promote renal cell carcinoma cell growth. Cell death & disease 32 31000693
1998 Glucocorticoids induce G1 as well as S-phase lengthening in normal human stimulated lymphocytes: differential effects on cell cycle regulatory proteins. Experimental cell research 32 9596999
2021 ASS1 and ASL suppress growth in clear cell renal cell carcinoma via altered nitrogen metabolism. Cancer & metabolism 30 34861885
2015 Structure-Activity Relationships of Neplanocin A Analogues as S-Adenosylhomocysteine Hydrolase Inhibitors and Their Antiviral and Antitumor Activities. Journal of medicinal chemistry 30 26010585
2024 β-Sitosterol targets ASS1 for Nrf2 ubiquitin-dependent degradation, inducing ROS-mediated apoptosis via the PTEN/PI3K/AKT signaling pathway in ovarian cancer. Free radical biology & medicine 29 38364944
2020 WRKY44 represses expression of the wound-induced sesquiterpene biosynthetic gene ASS1 in Aquilaria sinensis. Journal of experimental botany 29 31639819
2011 Activation of α7 nicotinic acetylcholine receptors persistently enhances hippocampal synaptic transmission and prevents Aß-mediated inhibition of LTP in the rat hippocampus. European journal of pharmacology 29 22200627
2020 lncRNA 00312 Attenuates Cell Proliferation and Invasion and Promotes Apoptosis in Renal Cell Carcinoma via miR-34a-5p/ASS1 Axis. Oxidative medicine and cellular longevity 28 32308805
2015 Tailoring the antibody response to aggregated Aß using novel Alzheimer-vaccines. PloS one 28 25611858
2011 RP-HPLC-ESI-MS evidenced that salivary cystatin B is detectable in adult human whole saliva mostly as S-modified derivatives: S-Glutathionyl, S-cysteinyl and S-S 2-mer. Journal of proteomics 28 22057043
2015 Vitamin E: Curse or Benefit in Alzheimer's Disease? A Systematic Investigation of the Impact of α-, γ- and δ-Tocopherol on Aß Generation and Degradation in Neuroblastoma Cells. The journal of nutrition, health & aging 27 26054501
2024 ASS1 enhances anoikis resistance via AMPK/CPT1A-mediated fatty acid metabolism in ovarian cancer. Cancer letters 25 38914306
2024 ASS1 inhibits triple-negative breast cancer by regulating PHGDH stability and de novo serine synthesis. Cell death & disease 24 38710705
2023 Downregulation of argininosuccinate synthase 1 (ASS1) is associated with hypoxia in placental development. Human cell 24 36995581
2022 A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma. Pigment cell & melanoma research 24 35466524
2024 ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response. Nature metabolism 23 38858597
2022 PGAM1 regulation of ASS1 contributes to the progression of breast cancer through the cAMP/AMPK/CEBPB pathway. Molecular oncology 23 35674458
2018 Aß Facilitates LTD at Schaffer Collateral Synapses Preferentially in the Left Hippocampus. Cell reports 23 29466733
2010 Two hypomorphic alleles of mouse Ass1 as a new animal model of citrullinemia type I and other hyperammonemic syndromes. The American journal of pathology 23 20724589
2022 Aß Pathology and Neuron-Glia Interactions: A Synaptocentric View. Neurochemical research 22 35976488
2017 Chromatin remodeling system p300-HDAC2-Sin3A is involved in Arginine Starvation-Induced HIF-1α Degradation at the ASS1 promoter for ASS1 Derepression. Scientific reports 22 28883660
2001 [Treatment of ASS-Associated Polyposis (ASSAP) with a cysteinyl leukotriene receptor antagonist - a prospective drug study on its antiinflammatory effects]. Laryngo- rhino- otologie 22 11602930
2011 Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells. Oncology reports 21 21424129
2021 Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1. EMBO reports 20 34184805
2020 Prolongation of metallothionein induction combats Aß and α-synuclein toxicity in aged transgenic Caenorhabditis elegans. Scientific reports 19 32678125
2018 Metabolomic profiling identifies distinct phenotypes for ASS1 positive and negative GBM. BMC cancer 19 29422017
2019 Nocardioides yefusunii sp. nov., isolated from Equus kiang (Tibetan wild ass) faeces. International journal of systematic and evolutionary microbiology 18 31511125
2010 A highly sensitive peptide substrate for detecting two Aß-degrading enzymes: neprilysin and insulin-degrading enzyme. Journal of neuroscience methods 18 20435063
2021 Phase 1, pharmacogenomic, dose-expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1-deficient non-squamous non-small cell lung cancer. Cancer medicine 17 34382365
2014 Aggregation of Aß(25-35) on DOPC and DOPC/DHA bilayers: an atomic force microscopy study. PloS one 17 25551704
2011 Association of plasma Aß peptides with blood pressure in the elderly. PloS one 17 21525986
2022 Insulin-like growth factor 5 associates with human Aß plaques and promotes cognitive impairment. Acta neuropathologica communications 16 35513854
2015 Metagenomic sequence of saline desert microbiota from wild ass sanctuary, Little Rann of Kutch, Gujarat, India. Genomics data 15 26484162
2014 Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass. Pakistan journal of pharmaceutical sciences 15 25410062
2011 Mitochondrial genome sequence of the Tibetan wild ass (Equus kiang). Mitochondrial DNA 15 21732718
2020 Down Regulation of SIRT2 Reduced ASS Induced NSCLC Apoptosis Through the Release of Autophagy Components via Exosomes. Frontiers in cell and developmental biology 14 33344455
2017 Taming the late Quaternary phylogeography of the Eurasiatic wild ass through ancient and modern DNA. PloS one 14 28422966
2002 Controlling Lewis basicity in polythioarsenate fluxes: stabilization of KSnAsS(5) and K(2)SnAs(2)S(6). Extended chains and slabs based on pyramidal beta-[AsS(4)](3-) and [AsS(3)](3-) units. Inorganic chemistry 14 12099862
2022 FXR/ASS1 axis attenuates the TAA-induced liver injury through arginine metabolism. Biochemical and biophysical research communications 13 35477090
2014 Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors. Endocrine-related cancer 13 25121552
2023 BAP1 Loss Is Associated with Higher ASS1 Expression in Epithelioid Mesothelioma: Implications for Therapeutic Stratification. Molecular cancer research : MCR 12 36669126
2022 Hepatocyte-derived MANF mitigates ethanol-induced liver steatosis in mice via enhancing ASS1 activity and activating AMPK pathway. Acta pharmacologica Sinica 12 35655095
2011 Inhibition of LPS toxicity by hepatic argininosuccinate synthase (ASS): novel roles for ASS in innate immune responses to bacterial infection. International immunopharmacology 12 21481813
2020 Use of Immunohistochemical Markers (HNF-1β, Napsin A, ER, CTH, and ASS1) to Distinguish Endometrial Clear Cell Carcinoma From Its Morphologic Mimics Including Arias-Stella Reaction. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 11 31094885
2018 Amino Acid Uptake Measured by [18F]AFETP Increases in Response to Arginine Starvation in ASS1-Deficient Sarcomas. Theranostics 11 29721066
2017 PRMT7 Interacts with ASS1 and Citrullinemia Mutations Disrupt the Interaction. Journal of molecular biology 11 28587924
2016 Genomic variants in the ASS1 gene, involved in the nitric oxide biosynthesis and signaling pathway, predict hydroxyurea treatment efficacy in compound sickle cell disease/β-thalassemia patients. Pharmacogenomics 11 26895070
2014 Functional analysis of novel splicing and missense mutations identified in the ASS1 gene in classical citrullinemia patients. Clinica chimica acta; international journal of clinical chemistry 11 25179242
1998 Chromosomal rearrangements in a Somali wild ass pedigree, Equus africanus somaliensis (Perissodactyla, Equidae). Cytogenetics and cell genetics 11 9678344
2022 Asymptomatic ASS1 carriers with high blood citrulline levels. Molecular genetics & genomic medicine 10 35726796
2021 Intracellular arginine-dependent translation sensor reveals the dynamics of arginine starvation response and resistance in ASS1-negative cells. Cancer & metabolism 10 33478587
2019 Citrullinemia type I is associated with a novel splicing variant, c.773 + 4A > C, in ASS1: a case report and literature review. BMC medical genetics 10 31208364
2019 Pre-plaque Aß-Mediated Impairment of Synaptic Depotentiation in a Transgenic Rat Model of Alzheimer's Disease Amyloidosis. Frontiers in neuroscience 10 31474823
2018 Argininosuccinate Synthetase-1 (ASS1) Loss in High-Grade Neuroendocrine Carcinomas of the Urinary Bladder: Implications for Targeted Therapy with ADI-PEG 20. Endocrine pathology 10 29453600
2017 Chryseobacterium salipaludis sp. nov., isolated at a wild ass sanctuary. International journal of systematic and evolutionary microbiology 10 29256852
2014 Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy. Journal of cancer research and clinical oncology 10 25548129
2013 Prenatal diagnosis of citrullinemia type 1: a Chinese family with a novel mutation of the ASS1 gene. Brain & development 10 23611581
2009 Citrullinemia type I, classical variant. Identification of ASS-p~G390R (c.1168G>A) mutation in families of a limited geographic area of Argentina: a possible population cluster. Clinical biochemistry 10 19358837
2009 Gut immune balance is as easy as S-F-B. Immunity 10 19833084
2004 Early cirrhosis in a patient with type I citrullinaemia (CTLN1). Journal of inherited metabolic disease 10 15334737
2023 Polymorphic Variants of ASS1 Gene Related to Arginine Metabolism and the Risk of HCC. Protein and peptide letters 9 37254538
2015 Reassessing the evolutionary history of ass-like equids: insights from patterns of genetic variation in contemporary extant populations. Molecular phylogenetics and evolution 9 25681678
2010 Reduced expression of ASS is closely related to clinicopathological features and post-resectional survival of hepatocellular carcinoma. Oncology letters 9 22966251