Affinage

ANTXR1

Anthrax toxin receptor 1 · UniProt Q9H6X2

Round 2 corrected
Length
564 aa
Mass
62.8 kDa
Annotated
2026-04-28
130 papers in source corpus 16 papers cited in narrative 16 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANTXR1 (TEM8) is a type I transmembrane receptor that couples extracellular matrix sensing to intracellular signaling, functioning in ECM homeostasis, angiogenesis, and Wnt/β-catenin pathway activation. Its extracellular von Willebrand factor A (vWA) domain binds anthrax toxin protective antigen, collagen VI fragment C5A, collagen I/IV, and laminin; ligation by C5A activates Wnt signaling through LRP6 upregulation and GSK3 phosphorylation, promoting stem cell self-renewal, invasion, and metastasis (PMID:11700562, PMID:23832666). At the cell surface, ANTXR1 conformation is regulated by actin cytoskeleton components (α-SMA, transgelin), and its endocytosis proceeds through a regulated sequence of palmitoylation-controlled lipid-raft entry and Cbl-mediated ubiquitination, with LRP6 as a co-internalization partner (PMID:16401723, PMID:16564009, PMID:21129411). Loss-of-function mutations in ANTXR1 cause GAPO syndrome, a disorder of generalized ECM dysregulation characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment (PMID:23602711).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2001 High

    Identification of ANTXR1 as the cellular receptor for anthrax toxin protective antigen established that a host transmembrane protein with an integrin-like vWA domain mediates toxin entry, opening the question of how receptor trafficking is regulated and what physiological ligands the receptor recognizes.

    Evidence Genetic complementation cloning in CHO cells plus direct binding of recombinant vWA domain to PA

    PMID:11700562

    Open questions at the time
    • Physiological ligands of ANTXR1 unknown at this stage
    • Mechanism of receptor endocytosis uncharacterized
    • Relationship to angiogenesis only correlative from TEM8 name
  2. 2006 High

    The discovery that palmitoylation prevents premature lipid-raft association and that Cbl-mediated ubiquitination in rafts triggers endocytosis revealed a two-step trafficking switch controlling ANTXR1 surface residence and toxin internalization.

    Evidence Palmitoylation-defective mutants, raft fractionation, Cbl co-IP, and ubiquitination assays in transfected cells

    PMID:16401723

    Open questions at the time
    • Palmitoyl transferase identity not determined
    • Whether this trafficking mechanism operates for physiological ligands unclear
  3. 2006 High

    Demonstration that LRP6 forms a physical complex with ANTXR1 and is required for PA internalization and lethality revealed a multicomponent receptor platform, linking ANTXR1 to the Wnt co-receptor machinery.

    Evidence RNAi, dominant-negative LRP6, anti-LRP6 antibody blocking, and reciprocal co-IP in multiple cell lines

    PMID:16564009

    Open questions at the time
    • Whether ANTXR1–LRP6 interaction has signaling consequences beyond toxin entry was unknown
    • Stoichiometry and structural basis of the complex unresolved
  4. 2010 High

    The 1.7 Å crystal structure of the ANTXR1 vWA domain confirmed an integrin-like fold and, combined with mutagenesis, pinpointed Leu56 and residues 154–160 as determinants of lower PA-binding affinity relative to CMG2, providing a structural framework for selective ligand recognition.

    Evidence X-ray crystallography and structure-guided mutagenesis with binding affinity measurements

    PMID:17251181 PMID:20585457

    Open questions at the time
    • No co-crystal with PA or ECM ligands solved
    • How structural differences translate to differential physiological functions of ANTXR1 vs CMG2 not established
  5. 2010 Medium

    Showing that α-smooth muscle actin and transgelin alter ANTXR1 extracellular domain conformation established that the intracellular actin cytoskeleton allosterically regulates receptor accessibility, analogous to inside-out signaling in integrins.

    Evidence Overexpression of actin-binding proteins with conformation-sensitive antibody readout and immunotoxin killing assays

    PMID:21129411

    Open questions at the time
    • Mechanism of transmembrane conformational coupling not defined
    • Physiological triggers for this conformational switch unknown
    • Single-lab observation without independent replication
  6. 2012 High

    Genetic ablation of Tem8 in mice showed it is required for pathological angiogenesis and tumor xenograft growth but dispensable for normal vascular homeostasis, establishing ANTXR1 as a selective driver of tumor-associated neovasculature.

    Evidence Tem8-knockout mice; xenograft tumor assays across multiple tumor types; anti-TEM8 antibody treatment

    PMID:22340594

    Open questions at the time
    • The endogenous ligand driving tumor angiogenesis through TEM8 was not identified in this study
    • Whether angiogenic role is cell-autonomous to endothelium vs stromal unclear
  7. 2013 High

    Identification of homozygous loss-of-function ANTXR1 mutations as the cause of GAPO syndrome demonstrated that the receptor's ECM-binding function is essential for normal tissue development and matrix homeostasis in humans.

    Evidence Whole-exome sequencing of multiple unrelated GAPO families; nonsense and splicing mutations validated by mRNA decay analysis

    PMID:23602711

    Open questions at the time
    • Precise ECM substrates whose processing is disrupted in GAPO syndrome not defined
    • No animal model recapitulating GAPO features described at this point
  8. 2013 Medium

    Demonstrating that collagen VI fragment C5A activates ANTXR1-dependent Wnt/β-catenin signaling (via LRP6 upregulation and GSK3 phosphorylation) to drive breast cancer stem cell self-renewal and metastasis unified the receptor's ECM-binding and LRP6-interacting activities into a coherent oncogenic signaling axis.

    Evidence C5A ligand stimulation, RNAi silencing, mammosphere assays, Wnt pathway readouts, and in vivo tumorigenicity/metastasis models

    PMID:23832666

    Open questions at the time
    • Whether C5A–ANTXR1–Wnt axis operates outside breast cancer not tested
    • Downstream transcriptional program beyond LRP6/ZEB1 not fully mapped
    • Direct mechanism linking ANTXR1 ligation to LRP6 upregulation unclear
  9. 2017 Medium

    Validation of ANTXR1 as a direct target of miR-493 and miR-26b-3p, with rescue experiments showing ANTXR1 activates Wnt/β-catenin signaling in hepatocellular carcinoma and promotes glioma cell proliferation, extended the oncogenic role of ANTXR1 beyond breast cancer.

    Evidence 3′UTR luciferase reporters, ORF rescue experiments, proliferation/migration/xenograft assays in HCC and glioma cells

    PMID:28651234 PMID:31934301

    Open questions at the time
    • Downstream Wnt targets in HCC/glioma contexts not deeply characterized
    • Single-lab studies without independent replication
  10. 2024 Medium

    Identification of ANTXR1 as a marker of ECM-producing myofibroblastic CAFs (ECM-myCAF) that suppress CD8+ T-cell cytotoxicity through YAP1-dependent signaling revealed a stromal immunosuppressive function for ANTXR1-expressing cells in the tumor microenvironment.

    Evidence Single-cell and spatial transcriptomics; functional co-culture of ECM-myCAF with CD8+ T cells; YAP1 inhibition rescue

    PMID:38346978

    Open questions at the time
    • Whether ANTXR1 itself signals through YAP1 or is merely a marker of this CAF subpopulation not resolved
    • Causal role of ANTXR1 in the immunosuppressive phenotype not tested by direct ANTXR1 perturbation in CAFs

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of ANTXR1 engagement with ECM ligands (no co-crystal exists), the direct mechanism coupling ANTXR1 ligation to LRP6-dependent Wnt activation, the identity of the palmitoyl transferase that modifies ANTXR1, and whether ANTXR1 plays a cell-autonomous signaling role in cancer-associated fibroblasts versus serving as a lineage marker.
  • No ANTXR1–ECM ligand co-crystal structure
  • Palmitoyl transferase identity unknown
  • ANTXR1 → LRP6/Wnt signaling mechanism not fully reconstituted
  • Cell-autonomous function in CAF immunosuppression not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-1474244 Extracellular matrix organization 2 GO:0005886 plasma membrane 1
Partners
ACTA2CBLCOL6A3LRP6TAGLN

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 ANTXR1 (ATR/TEM8) was identified as the cellular receptor for anthrax toxin protective antigen (PA). It is a type I membrane protein with an extracellular von Willebrand factor A (vWA) domain that directly binds PA, and a soluble version of this domain protects cells from anthrax toxin. Genetic complementation cloning; direct binding assay between recombinant vWA domain and PA; cell protection assay Nature High 11700562
2006 ANTXR1 undergoes palmitoylation in its cytoplasmic tail, which prevents premature association with lipid rafts and premature ubiquitination. Upon PA heptamerization, ANTXR1 moves into rafts where the E3 ubiquitin ligase Cbl ubiquitinates it, triggering rapid endocytosis of the toxin-receptor complex. Palmitoylation-defective receptors show reduced surface expression and premature internalization without PA heptamerization. Palmitoylation-defective mutant receptors; lipid raft fractionation; co-immunoprecipitation of Cbl; ubiquitination assays; endocytosis assays; cell intoxication assays The Journal of cell biology High 16401723
2006 LRP6 (a Wnt co-receptor) is required for anthrax toxin lethality and physically interacts with ANTXR1 (TEM8) at the cell surface to form a multicomponent complex that internalizes PA-containing toxin complexes. Downregulation of LRP6 or expression of dominant-negative LRP6 inhibited cellular uptake of PA and protected cells from death. RNAi knockdown of LRP6; dominant-negative LRP6 overexpression; anti-LRP6 antibody blocking; fluorescence microscopy; co-immunoprecipitation; biochemical fractionation Cell High 16564009
2007 ANTXR1 (TEM8) interacts with M2 isoenzyme of pyruvate kinase (M2-PK). An engineered TEM8-Fc molecule suppressed growth and metastasis of xenograft human tumors, potentially by trapping M2-PK. Co-immunoprecipitation identifying M2-PK as TEM8-interacting partner; xenograft tumor growth assays with TEM8-Fc Journal of the National Cancer Institute Low 17925540
2007 Specific residues in ANTXR1 TEM8's extracellular domain (residues 56, 57, and 154–160) determine the lower PA-binding affinity of TEM8 compared to CMG2. In particular, Leu56 is a key determinant of lower affinity. PA domain 4 variants (R659S/M662R) with preferential binding to TEM8 showed selective tumoricidal activity. Structure-based mutagenesis of TEM8; cell cytotoxicity assays with CHO cells expressing TEM8 vs CMG2; phage display selection of PA variants The Journal of biological chemistry Medium 17251181
2010 The crystal structure of the TEM8/ANTXR1 extracellular vWA domain was determined at 1.7 Å resolution. The domain adopts an integrin fold similar to CMG2. Structure-based mutagenesis identified the putative PA interface (residues 56, 57, 154–160) as responsible for the lower PA-binding affinity of TEM8 versus CMG2; Leu56 is the key residue. X-ray crystallography (1.7 Å resolution); structure-based mutagenesis; binding affinity assays PloS one High 20585457
2010 The cell-surface structure of ANTXR1 (TEM8) is regulated by the actin cytoskeleton. Alpha-smooth muscle actin and transgelin (an actin-binding protein) alter the conformation of TEM8 at the cell surface, converting it from an antibody-accessible (SB5-exposed) to an antibody-masked form, indicating that intracellular actin cytoskeleton components modulate TEM8 extracellular domain presentation. Overexpression of actin-binding proteins; antibody recognition assays (SB5 vs AF334 antibodies); immunotoxin killing assays distinguishing TEM8 conformations Biochimica et biophysica acta Medium 21129411
2011 ANTXR1 (TEM8) binds extracellular matrix proteins including collagen I, collagen IV, and laminin via its extracellular domain, and regulates endothelial cell migration and tubule formation during angiogenesis. CMG2 (ANTXR2) by contrast regulates endothelial proliferation. ECM binding assays; endothelial cell functional assays (migration, tubule formation); comparison of TEM8 and CMG2 loss-of-function Frontiers in bioscience (Landmark edition) Low 21196249
2012 Genetic disruption of Tem8/ANTXR1 impairs growth of human tumor xenografts. Anti-TEM8 antibodies blocked anthrax intoxication, inhibited tumor-induced angiogenesis, and displayed antitumor activity. TEM8 is required for pathological angiogenesis but its loss in normal tissues causes minimal toxicity, indicating a selective role in tumor vasculature. Genetic knockout mouse model (Tem8-null); xenograft tumor growth assays; antibody blockade experiments; anthrax intoxication protection assay Cancer cell High 22340594
2013 Loss-of-function mutations in ANTXR1 (nonsense and splicing mutations causing nonsense-mediated mRNA decay or truncated protein) cause GAPO syndrome, characterized by growth retardation, alopecia, pseudoanodontia, and progressive visual impairment. The phenotype reflects a generalized defect in extracellular matrix homeostasis, consistent with ANTXR1's role in ECM regulation. Whole-exome sequencing of affected individuals; identification of homozygous nonsense (p.Arg88*, p.Arg169*) and splicing (c.1435-12A>G) mutations; mRNA decay analysis; genotype-phenotype correlation American journal of human genetics High 23602711
2013 ANTXR1 acts as a functional biomarker of breast cancer stem-like cells. Activation of ANTXR1 by its natural ligand C5A (a collagen VI α3 fragment) increases stem cell self-renewal and activates Wnt signaling including upregulation of LRP6, phosphorylation of GSK3α/β, and elevated Wnt target genes. RNAi silencing of ANTXR1 reduces Wnt signaling (LRP6, ZEB1 expression), self-renewal, invasion, tumorigenicity, and metastasis. RNAi-mediated silencing; ligand stimulation (C5A peptide); mammosphere assay; Wnt pathway readouts (LRP6, GSK3 phosphorylation, target gene expression); in vivo tumorigenicity and metastasis assays Cancer research Medium 23832666
2018 Seneca Valley Virus (SVV) exploits ANTXR1 (TEM8) as an entry receptor, the same receptor used by anthrax toxin protective antigen. TEM8 also serves as a receptor for collagen VI, with the collagen VI interaction relevant to tumor cell biology. Receptor identification studies; cell entry assays; competitive binding with collagen VI and anthrax PA Frontiers in oncology Low 30460197
2017 MicroRNA-493 directly targets and suppresses ANTXR1 expression in hepatocellular carcinoma cells. ANTXR1 overexpression can rescue the tumor-suppressive effects of miR-493, and ANTXR1 activates Wnt/β-catenin signaling in HCC cells to promote proliferation, migration, and tumor formation. miR-493 overexpression; 3'UTR luciferase reporter validation; ANTXR1 rescue (ORF reintroduction); cell proliferation, colony formation, migration, invasion assays; xenograft tumor assay; Wnt pathway readouts Biomedicine & pharmacotherapy Medium 28651234
2019 MicroRNA-26b-3p directly targets ANTXR1 in glioma cells. ANTXR1 functions downstream of miR-26b-3p to promote glioma cell proliferation and migration and inhibit apoptosis; reintroduction of ANTXR1 (ORF lacking miRNA target site) rescues these effects. miR-26b-3p overexpression and inhibition; ORF rescue experiment; cell proliferation, migration, apoptosis assays; correlation with glioma severity American journal of translational research Medium 31934301
2021 N-Myc promotes angiogenesis and therapeutic resistance in prostate cancer via ANTXR1 (TEM8). N-Myc overexpression increases TEM8 expression, and combined overexpression promotes endothelial tubule formation and cancer cell proliferation; N-Myc-driven angiogenesis and resistance depend on TEM8. IHC correlation; overexpression of N-Myc and TEM8 in LNCaP cells; tubule formation assay with HUVECs; proliferation assays; bioinformatic analysis Medical oncology Low 34523032
2024 ANTXR1+ cancer-associated fibroblasts (ECM-myCAF cluster within CAF-S1) reduce CD8+ T-cell cytotoxicity through a YAP1-dependent mechanism. These ANTXR1+ ECM-producing myofibroblasts are the CAF-S1 subpopulation most reduced by chemotherapy; functional assays demonstrate that ECM-myCAF suppress CD8+ T-cell killing via YAP1 signaling. Single-cell RNA sequencing; spatial transcriptomics; immunohistochemistry; functional co-culture assays of ECM-myCAF with CD8+ T cells; YAP1 inhibition experiments Nature communications Medium 38346978

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2000 Genes expressed in human tumor endothelium. Science (New York, N.Y.) 1551 10947988
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2013 DNA damage sensing by the ATM and ATR kinases. Cold Spring Harbor perspectives in biology 1143 24003211
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1999 Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer research 919 10485486
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2013 ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 752 24267891
2001 Identification of the cellular receptor for anthrax toxin. Nature 720 11700562
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2017 The essential kinase ATR: ensuring faithful duplication of a challenging genome. Nature reviews. Molecular cell biology 658 28811666
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 TopBP1 activates the ATR-ATRIP complex. Cell 616 16530042
2003 Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor. Proceedings of the National Academy of Sciences of the United States of America 511 12700348
2001 ATM and ATR: networking cellular responses to DNA damage. Current opinion in genetics & development 509 11163154
2014 ATM and ATR as therapeutic targets in cancer. Pharmacology & therapeutics 504 25512053
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2000 Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes & development 410 11114888
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2001 Cell surface tumor endothelial markers are conserved in mice and humans. Cancer research 354 11559528
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2017 ATR/CHK1 inhibitors and cancer therapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 282 29054375
2018 Targeting ATR in cancer. Nature reviews. Cancer 267 29899559
2002 Hypoxia links ATR and p53 through replication arrest. Molecular and cellular biology 251 11865061
2018 An intrinsic S/G2 checkpoint enforced by ATR. Science (New York, N.Y.) 242 30139873
2010 ATR: a master conductor of cellular responses to DNA replication stress. Trends in biochemical sciences 226 20947357
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2002 Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. The Journal of biological chemistry 222 12435727
2015 Molecular Pathways: Targeting ATR in Cancer Therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 219 26362996
2018 SLFN11 Blocks Stressed Replication Forks Independently of ATR. Molecular cell 212 29395061
2007 The ATR pathway: fine-tuning the fork. DNA repair 202 17531546
2016 Activation of the ATR kinase by the RPA-binding protein ETAA1. Nature cell biology 200 27723717
2015 ATM and ATR signaling at a glance. Journal of cell science 193 26567218
2017 Targeting the ATR-CHK1 Axis in Cancer Therapy. Cancers 184 28448462
2006 Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis. The Journal of cell biology 163 16401723
2004 An unappreciated role for RNA surveillance. Genome biology 159 14759258
2013 Targeting ATR in DNA damage response and cancer therapeutics. Cancer treatment reviews 157 23583268
2017 Coupling of Homologous Recombination and the Checkpoint by ATR. Molecular cell 153 28089683
2007 ATM and ATR: components of an integrated circuit. Cell cycle (Georgetown, Tex.) 151 17312392
2016 Functions, Regulation, and Therapeutic Implications of the ATR Checkpoint Pathway. Annual review of genetics 147 27617969
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2012 TEM8/ANTXR1 blockade inhibits pathological angiogenesis and potentiates tumoricidal responses against multiple cancer types. Cancer cell 135 22340594
2002 Preferential binding of ATR protein to UV-damaged DNA. Proceedings of the National Academy of Sciences of the United States of America 132 12011431
2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine. Journal of proteomics 126 23376485
2010 The ATR barrier to replication-born DNA damage. DNA repair 120 21036674
2017 An Interaction Landscape of Ubiquitin Signaling. Molecular cell 119 28190767
1993 Ash/Grb-2, a SH2/SH3-containing protein, couples to signaling for mitogenesis and cytoskeletal reorganization by EGF and PDGF. The EMBO journal 118 8253073
2009 ATR/Mec1: coordinating fork stability and repair. Current opinion in cell biology 117 19230642
2017 APOBEC3A and APOBEC3B Activities Render Cancer Cells Susceptible to ATR Inhibition. Cancer research 113 28698210
2006 The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin. Cell 108 16564009
2001 UV-radiation induces dose-dependent regulation of p53 response and modulates p53-HDM2 interaction in human fibroblasts. Oncogene 107 11709713
2007 RPA and ATR link transcriptional stress to p53. Proceedings of the National Academy of Sciences of the United States of America 104 17616578
2013 ANTXR1, a stem cell-enriched functional biomarker, connects collagen signaling to cancer stem-like cells and metastasis in breast cancer. Cancer research 102 23832666
2021 Progress towards a clinically-successful ATR inhibitor for cancer therapy. Current research in pharmacology and drug discovery 101 34909652
2020 Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors. European urology 92 33176972
2021 TopBP1 assembles nuclear condensates to switch on ATR signaling. Molecular cell 90 33503405
2015 Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities. Cell reports 90 26748709
2018 Synthetically Lethal Interactions of ATM, ATR, and DNA-PKcs. Trends in cancer 88 30352678
2004 ATM and ATR: sensing DNA damage. World journal of gastroenterology 87 14716813
2019 A consensus set of genetic vulnerabilities to ATR inhibition. Open biology 84 31506018
2017 Cryo-EM structure of human ATR-ATRIP complex. Cell research 81 29271416
2017 DNA damage causes rapid accumulation of phosphoinositides for ATR signaling. Nature communications 79 29242514
1999 The association of ATR protein with mouse meiotic chromosome cores. Chromosoma 79 10382071
2024 Targeting ATR in patients with cancer. Nature reviews. Clinical oncology 72 38378898
2021 Clinical Candidates Targeting the ATR-CHK1-WEE1 Axis in Cancer. Cancers 71 33672884
2013 Mutations in ANTXR1 cause GAPO syndrome. American journal of human genetics 68 23602711
2004 Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation. Molecular biology of the cell 67 14767054
2016 Efficacy of ATR inhibitors as single agents in Ewing sarcoma. Oncotarget 66 27577084
2017 DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 28123024
2008 Activation of ATR and related PIKKs. Cell cycle (Georgetown, Tex.) 57 18769153
2023 Targeting ATM and ATR for cancer therapeutics: Inhibitors in clinic. Drug discovery today 56 37302542
2016 TPP1 Blocks an ATR-Mediated Resection Mechanism at Telomeres. Molecular cell 53 26778124
2022 Guiding ATR and PARP inhibitor combinationswith chemogenomic screens. Cell reports 52 35830811
2021 An extending ATR-CHK1 circuitry: the replication stress response and beyond. Current opinion in genetics & development 52 34329853
2019 Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer research 51 31273061
2019 Quantitative phosphoproteomics reveals mitotic function of the ATR activator ETAA1. The Journal of cell biology 50 30755469
2023 ATR promotes clearance of damaged DNA and damaged cells by rupturing micronuclei. Molecular cell 47 37788673
2003 Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites. American journal of physiology. Lung cellular and molecular physiology 47 12959929
2023 Emerging strategies for cancer therapy by ATR inhibitors. Cancer science 46 37189251
2004 A novel protein activity mediates DNA binding of an ATR-ATRIP complex. The Journal of biological chemistry 43 14724280
2022 TOP1-DNA Trapping by Exatecan and Combination Therapy with ATR Inhibitor. Molecular cancer therapeutics 42 35439320
2014 Homeostatic regulation of meiotic DSB formation by ATM/ATR. Experimental cell research 42 25116420
2011 Targeting the anthrax receptors, TEM-8 and CMG-2, for anti-angiogenic therapy. Frontiers in bioscience (Landmark edition) 41 21196249
2007 Antitumor activities of TEM8-Fc: an engineered antibody-like molecule targeting tumor endothelial marker 8. Journal of the National Cancer Institute 41 17925540
2010 Mechanisms of ATR-mediated checkpoint signalling. Frontiers in bioscience (Landmark edition) 40 20515729
2004 The ATR-p53 pathway is suppressed in noncycling normal and malignant lymphocytes. Oncogene 40 14755251
2016 ATR-mediated regulation of nuclear and cellular plasticity. DNA repair 38 27283761
2010 The cell surface structure of tumor endothelial marker 8 (TEM8) is regulated by the actin cytoskeleton. Biochimica et biophysica acta 38 21129411
2005 ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress. Biochemical and biophysical research communications 38 16004968
2024 Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway. Nature communications 37 38346978
2021 Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11. Cancers 37 34572827
2015 Wee1 is required to sustain ATR/Chk1 signaling upon replicative stress. Oncotarget 37 25965828
2020 Structures and regulations of ATM and ATR, master kinases in genome integrity. Current opinion in structural biology 35 31924595
2020 ATR Restrains DNA Synthesis and Mitotic Catastrophe in Response to CDC7 Inhibition. Cell reports 35 32877678
2013 DNA structure-specific priming of ATR activation by DNA-PKcs. The Journal of cell biology 35 23897887
2010 The structure of tumor endothelial marker 8 (TEM8) extracellular domain and implications for its receptor function for recognizing anthrax toxin. PloS one 35 20585457
2007 Selection of anthrax toxin protective antigen variants that discriminate between the cellular receptors TEM8 and CMG2 and achieve targeting of tumor cells. The Journal of biological chemistry 34 17251181
2019 Common motifs in ETAA1 and TOPBP1 required for ATR kinase activation. The Journal of biological chemistry 33 30940728
2008 ATR and Rad17 collaborate in modulating Rad9 localisation at sites of DNA damage. Journal of cell science 32 19020305
2020 ATR-Mediated FANCI Phosphorylation Regulates Both Ubiquitination and Deubiquitination of FANCD2. Frontiers in cell and developmental biology 30 32117957
2023 ATR protects ongoing and newly assembled DNA replication forks through distinct mechanisms. Cell reports 29 37454295
2009 Mouse models for ATR deficiency. DNA repair 29 19782648
2021 A Tale of Two Checkpoints: ATR Inhibition and PD-(L)1 Blockade. Annual review of medicine 28 34644155
2014 RAD50 phosphorylation promotes ATR downstream signaling and DNA restart following replication stress. Human molecular genetics 26 24694934
2010 Proapoptotic Bid mediates the Atr-directed DNA damage response to replicative stress. Cell death and differentiation 26 21113148
2023 ADAR1 links R-loop homeostasis to ATR activation in replication stress response. Nucleic acids research 25 37831098
2022 Therapeutic targeting of ATR in alveolar rhabdomyosarcoma. Nature communications 24 35879366
2018 Seneca Valley Virus Exploits TEM8, a Collagen Receptor Implicated in Tumor Growth. Frontiers in oncology 24 30460197
2017 MicroRNA-493 suppresses hepatocellular carcinoma tumorigenesis through down-regulation of anthrax toxin receptor 1 (ANTXR1) and R-Spondin 2 (RSPO2). Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 28651234
2018 Targeting ataxia telangiectasia-mutated- and Rad3-related kinase (ATR) in PTEN-deficient breast cancers for personalized therapy. Breast cancer research and treatment 23 29396668
2017 PHF11 promotes DSB resection, ATR signaling, and HR. Genes & development 23 28115467
2021 Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection. The EMBO journal 22 33764556
2014 Development of pharmacodynamic biomarkers for ATR inhibitors. Molecular oncology 22 25459351
2021 PHF8-promoted TOPBP1 demethylation drives ATR activation and preserves genome stability. Science advances 21 33952527
2020 Pathogenesis of Human Papillomaviruses Requires the ATR/p62 Autophagy-Related Pathway. mBio 21 32788179
2021 ATR-X syndrome: genetics, clinical spectrum, and management. Human genetics 20 34524523
2024 ATR blocks telomerase from converting DNA breaks into telomeres. Science (New York, N.Y.) 19 38359122
2022 Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy. Nucleic acids research 19 35524559
2021 Circadian Rhythm of NER and ATR Pathways. Biomolecules 19 34064641
2021 N-Myc promotes angiogenesis and therapeutic resistance of prostate cancer by TEM8. Medical oncology (Northwood, London, England) 19 34523032
2022 TEM8 Tri-specific Killer Engager binds both tumor and tumor stroma to specifically engage natural killer cell anti-tumor activity. Journal for immunotherapy of cancer 18 36162918
2021 ATR activation is regulated by dimerization of ATR activating proteins. The Journal of biological chemistry 18 33636182
2019 MicroRNA-26b-3p/ANTXR1 signaling modulates proliferation, migration, and apoptosis of glioma. American journal of translational research 18 31934301