Affinage

GAS1

Growth arrest-specific protein 1 · UniProt P54826

Length
345 aa
Mass
35.7 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAS1 is a GPI-anchored plasma membrane protein originally identified as a growth-arrest-specific gene that suppresses the G0-to-S transition and inhibits DNA synthesis when overexpressed in quiescent cells (PMID:1505026, PMID:10996315). Its antiproliferative output operates through a transactivation-independent function of p53 that requires the p53 proline-rich region (residues 63–85) as a docking site, and is independent of the GPI anchor itself (PMID:8524283, PMID:9114050, PMID:10996316). GAS1 functions broadly as a cell-surface co-receptor that tunes multiple developmental signaling pathways: it binds Sonic hedgehog (SHH) through a unique SHH surface distinct from the Patched-binding face and cooperates with Patched1/Ptch2, CDO and BOC to enhance HH pathway activity in a cell-autonomous manner, an activity obligatory for ventral neural tube patterning, craniofacial and skeletal development (PMID:17504940, PMID:17504941, PMID:19478089, PMID:21664576, PMID:21664577, PMID:32332736). Reduced SHH-GAS1 binding caused by SHH or GAS1 missense variants is a mechanistic basis for holoprosencephaly, and GAS1 genetically interacts with Shh as an HPE modifier (PMID:17525797, PMID:19478089, PMID:21842183). In parallel, GAS1 binds the RET receptor tyrosine kinase in a ligand-independent manner, sequesters it in lipid rafts, and attenuates GDNF-dependent RET/Shc/AKT survival signaling, driving intrinsic mitochondrial apoptosis through BAD dephosphorylation, cytochrome-c release, and caspase-9/3 activation (PMID:16551639, PMID:18394855, PMID:22311470). GAS1 additionally binds NOTCH1 to enhance ligand-induced intracellular-domain processing, sustaining NOTCH activity in forebrain neuroepithelium independently of its SHH co-receptor role (PMID:34698766). Across tissues GAS1 expression is set by context-specific transcriptional inputs—repressed by c-Myc and miR-34a, and induced by WT1, NOTCH4, Wnt/TCF4, and VE-cadherin/VEGF via PI3K—linking it to endothelial survival, nephron progenitor maintenance, myogenic differentiation, and cancer-cell quiescence (PMID:9371770, PMID:21820049, PMID:15070677, PMID:25804736, PMID:32104513, PMID:24220341, PMID:37533188). Through its p53 axis GAS1 also promotes ferroptosis via SLC7A11 repression in hepatic injury (PMID:37859699).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1992 High

    Established GAS1 as a functional growth suppressor rather than a passive marker of quiescence, defining the question of how a membrane protein blocks cell-cycle re-entry.

    Evidence Microinjection and overexpression in NIH 3T3 cells with immunofluorescence localization

    PMID:1505026

    Open questions at the time
    • Molecular effector of the arrest not identified
    • No partner protein implicated at this stage
  2. 1995 Medium

    Resolved how GAS1 arrest is transmitted intracellularly by showing it requires a transactivation-independent function of p53.

    Evidence Co-overexpression of GAS1 with p53 mutants and proliferation assays

    PMID:8524283

    Open questions at the time
    • Did not pinpoint the p53 domain involved
    • Mechanism of signal relay from membrane to p53 unknown
  3. 1997 High

    Mapped the p53 proline-rich region (aa 63–85) as the docking site for GAS1 antiproliferative signaling and identified c-Myc as a transcriptional repressor of GAS1, embedding it in proliferative control circuits.

    Evidence p53 deletion/point mutagenesis with competition assays; Myc-ER inducible reporter assays

    PMID:9114050 PMID:9371770

    Open questions at the time
    • No direct physical GAS1–p53 interaction demonstrated
    • How surface GAS1 communicates with nuclear p53 unresolved
  4. 2000 High

    Defined GAS1 biogenesis as a GPI-anchored outer-leaflet protein and showed the GPI anchor is dispensable for growth suppression, separating its membrane topology from its antiproliferative output.

    Evidence Immunoelectron microscopy, biochemical fractionation, and domain-deletion growth assays

    PMID:10996315 PMID:10996316

    Open questions at the time
    • Functional domain mediating arrest not delimited
    • Relationship between caveolar relocalization and signaling unclear
  5. 2003 Medium

    Placed GAS1 downstream of VE-cadherin/VEGF PI3K signaling as an effector of endothelial survival, expanding its role beyond growth arrest.

    Evidence Ectopic expression, siRNA, PI3K inhibition, and allantois organ culture in endothelial cells

    PMID:15070677

    Open questions at the time
    • Direct transcriptional mechanism of PI3K-driven induction not defined
    • Anti- versus pro-apoptotic context-dependence unexplained
  6. 2006 Medium

    Identified GAS1 as a ligand-independent RET-binding protein that sequesters RET in lipid rafts and rewires GDNF signaling, establishing a second receptor-modulatory function.

    Evidence Co-immunoprecipitation, lipid-raft fractionation, and Shc/ERK/Akt phosphorylation analysis

    PMID:16551639

    Open questions at the time
    • Direct binding interface not mapped
    • Reciprocal validation in vivo limited at this stage
  7. 2007 High

    Defined GAS1 as a positive HH co-receptor acting with Patched1 and CDO to shape the SHH activity gradient required for neural tube, craniofacial and vertebral patterning, and as an HPE modifier genetically interacting with Shh.

    Evidence Gas1 (and Cdo) single/compound knockout mice, ectopic expression, in vitro binding and in ovo electroporation

    PMID:17504940 PMID:17504941 PMID:17525797

    Open questions at the time
    • Structural basis of SHH–GAS1 binding not defined
    • Quantitative contribution to gradient shape vs. CDO/BOC unresolved
  8. 2009 Medium

    Confirmed GAS1 as a negative modulator of GDNF-RET signaling by showing it reduces RET Y1062 phosphorylation and AKT activation in neuroblastoma cells.

    Evidence Overexpression with phospho-RET and phospho-AKT immunoblotting in SH-SY5Y cells

    PMID:18394855

    Open questions at the time
    • Single cell line
    • Downstream apoptotic consequence not yet linked
  9. 2009 High

    Resolved the molecular basis of GAS1's HPE link by showing SHH presents a GAS1-binding surface distinct from the Patched surface, with the N115K HPE mutation selectively disrupting GAS1 binding.

    Evidence Cell-surface binding, explant culture, and SHH mutagenesis assays

    PMID:19478089

    Open questions at the time
    • GAS1 residues contacting SHH not mapped
    • No co-crystal structure
  10. 2011 High

    Established an obligatory, partly redundant requirement for GAS1, CDO and BOC as ligand-binding HH coreceptors and showed GAS1 and BOC form distinct Ptch1 complexes, defining the receptor architecture of HH signal reception.

    Evidence Single, double and triple knockout mice/neurons and HH ligand mutagenesis binding assays

    PMID:21664576 PMID:21664577 PMID:21842183

    Open questions at the time
    • Stoichiometry and structural organization of the coreceptor complexes unknown
    • How redundancy is partitioned across tissues unclear
  11. 2011 Medium

    Linked GAS1 to myogenic differentiation by showing it complexes with CDO and activates p38MAPK and cell-cycle arrest in differentiating myoblasts.

    Evidence Reciprocal Co-IP, knockdown/rescue, and p38MAPK/differentiation assays in C2C12 cells

    PMID:21820049

    Open questions at the time
    • Direct GAS1–CDO binding interface not mapped
    • Connection to HH signaling in muscle context not resolved
  12. 2012 Medium

    Connected GAS1-RET signaling to intrinsic apoptosis, defining the BAD/cytochrome-c/caspase-9/3 cascade as the effector of GAS1-mediated death.

    Evidence Caspase and cytochrome-c assays, phospho-RET/AKT/BAD immunoblotting, and siRNA knockdown

    PMID:22311470

    Open questions at the time
    • Single cell line
    • Relative contribution of p53 versus RET axes to apoptosis not dissected
  13. 2014 High

    Extended GAS1 to SHH-induced axon guidance, showing it acts as a Smo-dependent SHH receptor in enteric neurons signaling through the Gαi protein Gnaz.

    Evidence Neurosphere axon-turning assay, conditional knockout, and Gnaz knockdown/dominant-negative with intestinal phenotyping

    PMID:25535338

    Open questions at the time
    • How GAS1 couples to Gnaz mechanistically unknown
    • Generality of Smo-dependent repulsion beyond enteric neurons untested
  14. 2015 High

    Defined a transcriptional input (WT1) and a tissue role for GAS1 in nephron progenitor maintenance via FGF-stimulated AKT signaling.

    Evidence WT1 ChIP on the Gas1 promoter, Gas1 knockout mice, and FGF/AKT signaling assays

    PMID:25804736

    Open questions at the time
    • How GAS1 selectively gates FGF–AKT signaling unknown
    • Receptor partner in this context unidentified
  15. 2021 High

    Identified a distinct NOTCH1-facilitating function for GAS1, showing it binds NOTCH1 and enhances ICD processing to sustain NOTCH and SHH activity in forebrain neuroepithelium.

    Evidence Co-IP, GAS1 knockout mice, iPSC-derived neuroepithelial models, and NOTCH1 cleavage assays

    PMID:34698766

    Open questions at the time
    • Mechanism by which GAS1 promotes NOTCH cleavage unknown
    • Interplay between the NOTCH and SHH co-receptor functions not fully separated
  16. 2023 Medium

    Consolidated GAS1 as a context-dependent tumor and tissue regulator acting through its RET and p53 axes, including RET/AKT/mTOR suppression of cancer stemness and p53/SLC7A11-driven ferroptosis.

    Evidence ChIP, Co-IP (GAS1-RET), organoid and in vivo models; AAV overexpression/knockdown with ferroptosis readouts

    PMID:37824217 PMID:37859699

    Open questions at the time
    • Whether RET and p53 axes operate independently or convergently unresolved
    • Single-lab mechanistic models per cancer type

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single GPI-anchored surface protein integrates and switches between SHH co-receptor, RET-inhibitory, and NOTCH-facilitating functions in a tissue-specific manner remains unresolved.
  • No structural model of GAS1 with any partner
  • Determinants selecting among SHH/RET/NOTCH outputs unknown
  • Mechanism linking surface GAS1 to nuclear p53 signaling undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1640170 Cell Cycle 3
Partners
CDOGFRANOTCH1P53PTCH1PTCH2RETSHH
Complex memberships
GAS1–CDO complexGAS1–PTCH1 Hedgehog coreceptor complexGAS1–PTCH2 complexGAS1–RET complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 Gas1 is an integral plasma membrane protein whose expression is linked to growth arrest; overexpression in quiescent cells inhibits serum-induced G0-to-S phase transition without affecting early serum response, and microinjection into normal and transformed NIH 3T3 cells (except SV40-transformed) inhibits DNA synthesis, establishing Gas1 as a component of a negative circuit governing growth suppression. Microinjection, overexpression, immunofluorescence, in vitro translation Cell High 1505026
2000 The mammalian Gas1 protein is a GPI-anchored protein: it undergoes cotranslational signal peptide cleavage, N-linked glycosylation, and glycosyl-phosphatidylinositol anchor addition in the ER; in its mature form it is randomly distributed over the outer leaflet of the plasma membrane and upon antibody-induced clustering relocalizes to caveolae. Immunoelectron microscopy, biochemical fractionation, antibody-induced clustering FEBS letters High 10996315
1995 Gas1-induced growth arrest requires a transactivation-independent function of p53; the N-terminal transactivating domain of p53 is dispensable, implicating other p53 functions (related to apoptosis regulation) in mediating the antiproliferative signal. Overexpression of Gas1 with p53 mutants, proliferation assays Molecular and cellular biology Medium 8524283
1997 Gas1-dependent growth arrest signaling requires the proline-rich region (amino acids 63–85) of p53; deletional analysis and site-specific mutagenesis identified this domain as a docking site for transmission of antiproliferative signals from Gas1, acting in a transactivation-independent manner. Deletional analysis and site-specific mutagenesis of p53, in vivo competition experiments Proceedings of the National Academy of Sciences of the United States of America High 9114050
1997 c-Myc transcriptionally represses gas1 expression; Myc box 2 is required for this repression and for Myc-induced proliferation and transformation but not for activation of ODC. Activation of a Myc-ER fusion protein was sufficient to repress gas1 transcription. Reporter assays, Myc domain mutants, Myc-ER inducible system Proceedings of the National Academy of Sciences of the United States of America Medium 9371770
2006 Gas1 binds to the Ret receptor tyrosine kinase in a ligand-independent manner and sequesters Ret in lipid rafts; this modifies downstream Ret signaling via the adaptor protein Shc and ERK, ultimately blocking Akt activation and compromising GDNF-dependent survival effects. Gas1 shows structural similarity to GFRα co-receptors. Co-immunoprecipitation, lipid raft fractionation, signaling pathway analysis (Shc, ERK, Akt phosphorylation), sequence/structural analysis The Journal of biological chemistry Medium 16551639
2007 Gas1 acts as a positive regulator of Shh signaling by binding Shh and acting cooperatively with Patched1 for Hedgehog binding, enhancing signaling activity in a cell-autonomous manner; Gas1 helps transform the Hh concentration gradient into the activity gradient. Loss of Gas1 results in Shh dose-dependent loss of ventral neural tube cell identities and craniofacial/skeletal defects. Genetic loss-of-function (Gas1 knockout mice), ectopic expression, in vitro cell culture binding assays, in ovo electroporation Genes & development High 17504940 17504941
2007 Gas1 is a novel positive component of the Shh signaling cascade. Gas1 and Cdo cooperate to promote Shh signaling during neural tube patterning, craniofacial, and vertebral development. Gas1 expression is down-regulated by active Hh signaling, consistent with a feedback regulatory mechanism. Gas1 and Cdo single and double knockout mice, ectopic Gas1 expression, neural tube patterning assays Genes & development High 17504941
2007 Gas1 is a modifier for holoprosencephaly and genetically interacts with Shh: Gas1−/− mice exhibit microform HPE and craniofacial defects associated with partial loss of Shh signaling at a distance from the source, and loss of a single Shh allele in Gas1−/− background significantly exacerbates the midline craniofacial phenotype. Targeted Gas1 deletion mouse model, Shh haploinsufficiency genetic interaction, craniofacial phenotyping, Shh signaling analysis The Journal of clinical investigation High 17525797
2008 Gas1 reduces phosphorylation of Ret tyrosine 1062 in response to GDNF and significantly reduces Akt activation in SH-SY5Y neuroblastoma cells, acting as a negative modulator of GDNF-RET intracellular signaling. Overexpression in neuroblastoma cells, phospho-Ret and phospho-Akt immunoblotting International journal of developmental neuroscience Medium 18394855
2009 SHH contains a unique binding surface for GAS1 distinct from the Patched-binding surface; missense mutation N115K of human SHH (associated with HPE) severely reduces SHH binding to GAS1 without abrogating Patched1 binding, mechanistically linking this HPE mutation to loss of GAS1 interaction. Cell surface binding assays, in vitro activity assays, explant culture assays, mutagenesis The Journal of biological chemistry High 19478089
2011 GAS1, CDO, and BOC play overlapping and essential roles as HH coreceptors during ventral neural patterning. Genetic loss-of-function demonstrates an obligatory requirement for all three coreceptors in HH pathway activity in multiple tissues; they function in cell fate specification and motor neuron progenitor maintenance. Single and compound genetic knockouts in mice, neural tube patterning analysis Developmental cell High 21664576 21664577
2011 Boc and Gas1 each form distinct receptor complexes with Ptch1; cerebellar granule neuron progenitors lacking all three molecules (Boc, Cdon, Gas1) show complete loss of Hh-dependent proliferation. A mutated Hh ligand that binds Ptch1 but not Boc, Cdon, or Gas1 cannot activate Hh signaling, demonstrating an absolute requirement for these ligand-binding components in Hh signal transduction. Triple knockout neurons, Hh ligand mutagenesis binding assays, cerebellar granule neuron proliferation assays Developmental cell High 21664577
2011 GAS1 missense variants found in HPE patients reduce the affinity of GAS1 for its ligand SHH, as demonstrated by direct binding assays, providing a mechanistic explanation for GAS1's role in HPE pathogenesis. Direct SHH-GAS1 binding assays with patient-derived GAS1 variants Human genetics Medium 21842183
2011 Gas1 and Cdo are coexpressed in muscle cells and form a complex in differentiating myoblasts; Gas1 promotes myogenic differentiation by regulating cell cycle arrest (downregulation of Cdk2 and Cyclin D1, upregulation of miR-322) and activating p38MAPK downstream of Cdo. Gas1 overexpression in Cdo-depleted C2C12 cells restores p38MAPK activity and differentiation. Co-immunoprecipitation, overexpression/knockdown in myoblasts, p38MAPK phosphorylation assays, differentiation assays Cellular signalling Medium 21820049
2012 GAS1 induces apoptosis through an intrinsic (mitochondrial) pathway: GAS1 expression reduces Ret phosphorylation, inhibits Akt activation, triggers BAD dephosphorylation, causes cytochrome-c release from mitochondria, and activates caspase-9 and caspase-3 without activating caspase-8. Silencing GAS1 significantly delays apoptosis onset. Caspase activity assays, cytochrome-c release assay, phospho-Ret/Akt/BAD immunoblotting, siRNA knockdown Apoptosis Medium 22311470
2003 Gas1 is induced by VE-cadherin and VEGF in endothelial cells; this induction requires PI3-kinase activation. Ectopic Gas1 expression strongly reduces apoptosis in endothelial cells, and siRNA-mediated Gas1 inhibition makes endothelial cells refractory to VEGF's antiapoptotic effect, positioning Gas1 downstream of the PI3K pathway as an effector of endothelial survival. Syngenic cell line comparison, ectopic expression, siRNA knockdown, PI3K inhibition (Wortmannin), VE-cadherin blocking antibody, allantois organ culture Blood Medium 15070677
2014 Gas1 is a receptor for Sonic hedgehog (Shh) in enteric neurons and mediates Shh-induced axon repulsion; Shh binding to Gas1 requires smoothened (Smo) for signaling, and the Gαi protein Gnaz (found in enteric axons) is a downstream effector of this pathway—knockdown or dominant-negative inhibition of Gnaz dampens axon-repulsive responses to Shh. In vitro neurosphere axon turning assay, Gas1 conditional knockout, Gnaz knockdown/dominant-negative, intestinal phenotyping Proceedings of the National Academy of Sciences of the United States of America High 25535338
2015 WT1 directly binds to a conserved DNA binding motif in the Gas1 promoter and activates Gas1 transcription in nephron progenitor cells; Gas1 is selectively required for FGF-stimulated AKT signaling in vitro, and Gas1 knockout causes hypoplastic kidneys with premature nephron progenitor depletion. ChIP (WT1 binding to Gas1 promoter), Gas1 knockout mice, FGF signaling assays (AKT phosphorylation) Development (Cambridge, England) High 25804736
2019 Gas1 reduces Ret signaling in muscle stem cells (MuSCs), impairing their quiescence and self-renewal capacity; GDNF counteracts Gas1 by stimulating Ret signaling to enhance MuSC self-renewal and regeneration. Gas1 expression progressively increases in MuSCs with age, contributing to regenerative decline. Gas1 overexpression and inactivation in MuSCs, Ret signaling assays, muscle regeneration assays in vivo Nature metabolism Medium 32021964
2020 NOTCH4 transcriptionally upregulates GAS1 by directly binding to conserved sites in the GAS1 promoter (demonstrated by dual-luciferase reporter and ChIP assays), promoting quiescence of mesenchymal-like breast cancer stem cells in TNBC. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP), RNA-seq, lentiviral overexpression/knockdown Theranostics Medium 32104513
2020 Parkin directly interacts with GATA4 (shown by co-immunoprecipitation) and promotes its ubiquitination, leading to decreased GATA4 protein levels; GATA4 overexpression enhances high-glucose-induced GAS1 expression, and GAS1 overexpression mitigates the protective effects of Parkin on renal tubular epithelial cells, placing GAS1 downstream of the Parkin-GATA4 axis. Co-immunoprecipitation, ubiquitination assay, overexpression/knockout in mice and cells, western blot FASEB journal Medium 32436607
2020 Gas1 and Ptch2 form a specific heteromeric complex that mediates Hedgehog signaling with different kinetics from Ptch1/Boc; Ptch2-mediated Hedgehog signaling induces phosphorylation of Creb and Src in parallel to Gli induction, identifying a Ptch2-specific signal pathway in which Gas1 spatiotemporally determines the outcome. Genetic compound mutants (primordial germ cell migration model), signaling assays (Creb and Src phosphorylation), Gli induction assays Nature communications Medium 32332736
2021 GAS1 directly binds NOTCH1 and enhances ligand-induced processing of the NOTCH1 intracellular domain, thereby facilitating NOTCH pathway activity in the developing forebrain neuroepithelium; this NOTCH-facilitation function is required to sustain SHH activity domain and is distinct from Gas1's direct role as a Shh co-receptor. Co-immunoprecipitation (GAS1-NOTCH1 binding), GAS1 knockout mice, iPSC-derived neuroepithelial models, NOTCH1 cleavage/processing assays Development (Cambridge, England) High 34698766
2000 Gas1 growth-suppression function does not require its GPI anchor; domain analysis demonstrates that the GPI anchor is dispensable for the antiproliferative activity of Gas1. Domain deletion/mutagenesis constructs, growth arrest assays FEBS letters Medium 10996316
2002 Gas1 is induced in neurons committed to die after NMDA exposure; overexpression of Gas1 in hippocampal neurons produces marked cell death; Gas1-induced neuronal death is attenuated by Bcl-2 or the caspase inhibitor OpIAP2; OpIAP2 co-immunoprecipitates with Gas1, suggesting a direct interaction. Differential screening, overexpression, antisense inhibition, Bcl-2 co-expression, caspase inhibitor treatment, co-immunoprecipitation Molecular and cellular neurosciences Medium 11906213
2013 miR-34a directly targets the 3'-UTR of GAS1 mRNA, repressing GAS1 expression; miR-34a overexpression in papillary thyroid carcinoma cells promotes proliferation and inhibits apoptosis via activation of PI3K/Akt/Bad signaling, and these effects are phenocopied by GAS1 silencing. Luciferase 3'-UTR reporter assay, miR-34a overexpression/knockdown, GAS1 siRNA, Akt inhibitor rescue Biochemical and biophysical research communications Medium 24220341
2016 Gas1 negatively regulates aerobic glycolysis in colorectal cancer cells by decreasing transcription of key glycolytic enzymes (GLUT4, HK2, LDHB) and inhibiting the AMPK/mTOR/p70S6K signaling axis; Gas1 is itself a transcriptional target of FOXM1. Gas1 overexpression/knockdown in colorectal cancer cells, PET/CT in vivo, glycolytic enzyme expression, AMPK/mTOR/p70S6K pathway analysis, FOXM1 ChIP/reporter Molecular cancer research Medium 27401611
2020 Wnt/β-catenin signaling activates GAS1 expression in CD143+ cancer-associated fibroblasts; TCF4 directly regulates GAS1 transcription as shown by ChIP-qPCR, and GAS1-expressing CD143+ CAFs suppress colorectal tumorigenesis. ChIP-qPCR (TCF4 binding to GAS1), scRNA-seq, western blot, in vivo tumor models Cancer communications Medium 37533188
2023 ATOH1 deficiency downregulates GAS1 by suppressing GAS1 promoter transcription; GAS1 forms a complex with RET and inhibits Tyr1062 phosphorylation; loss of GAS1 consequently activates the RET/AKT/mTOR signaling pathway, promoting cancer stemness in gastric adenocarcinoma. ChIP (ATOH1 at GAS1 promoter), co-immunoprecipitation (GAS1-RET complex), phospho-Ret immunoblotting, organoid models, in vivo mouse models Advanced science Medium 37824217
2023 GAS1 overexpression promotes ferroptosis in liver cells during acetaminophen-induced acute liver failure via p53, which inhibits the downstream target SLC7A11 (solute carrier family 7 member 11), leading to lipid peroxide accumulation; ferroptosis inhibitor ferrostatin-1 and GAS1 knockdown both alleviate this damage. Liver-specific GAS1 AAV overexpression mice, shRNA knockdown in hepatocytes, ferrostatin-1 treatment, lipid peroxide/ROS/GSH assays International journal of medical sciences Medium 37859699
2014 A soluble form of GAS1 (tGAS1) inhibits triple-negative breast cancer growth via a RET-independent mechanism involving interference with Artemin-GFRα3-mediated ERK signaling, and also reduces tumor vascularization by preventing endothelial cell migration. Soluble GAS1 (tGAS1) treatment of MDA-MB-231 cells and nude mouse xenograft, ERK activation assays, endothelial migration assay Experimental cell research Medium 24992044
2012 Gas1 mutant gastrointestinal tract shows reduced Hh signaling (shorter GI tract, thinner smooth muscles) phenocopying Shh mutants, and also shows increased phospho-Ret, phospho-Akt, and phospho-Erk in enteric progenitors; Gas1 thus balances Hh and Ret signaling in the GI tract. Gas1 knockout mouse GI phenotyping, phospho-Ret/Akt/Erk immunoblotting in isolated enteric progenitors Biology open Medium 23429478
2017 GAS1 promotes ferroptosis-related cell death via a p53/SLC7A11 axis (corroborated across publications); additionally, GAS1 upregulation is induced in reactive astrocytes by LPS/IFN-γ/TNF-α treatment and contributes to their apoptosis via increased Bax/Bcl-2 ratio, ROS generation, and caspase-3 activation; siRNA knockdown of GAS1 confirms this role. siRNA knockdown of Gas1 in astrocytes, CCK-8 viability, flow cytometry, TUNEL, Bax/Bcl-2 immunoblotting, ROS assay Journal of neuroinflammation Medium 27391369

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1992 The growth arrest-specific gene, gas1, is involved in growth suppression. Cell 270 1505026
2011 Overlapping roles and collective requirement for the coreceptors GAS1, CDO, and BOC in SHH pathway function. Developmental cell 227 21664576
2007 The Hedgehog-binding proteins Gas1 and Cdo cooperate to positively regulate Shh signaling during mouse development. Genes & development 224 17504941
1991 Determinants for glycophospholipid anchoring of the Saccharomyces cerevisiae GAS1 protein to the plasma membrane. Molecular and cellular biology 204 1824714
2011 Boc and Gas1 each form distinct Shh receptor complexes with Ptch1 and are required for Shh-mediated cell proliferation. Developmental cell 198 21664577
2007 Gas1 extends the range of Hedgehog action by facilitating its signaling. Genes & development 174 17504940
1999 The Gas1 glycoprotein, a putative wall polymer cross-linker. Biochimica et biophysica acta 155 9878845
2001 Mitochondrial expression and function of GAS-1 in Caenorhabditis elegans. The Journal of biological chemistry 141 11278828
1999 GAS-1: a mitochondrial protein controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans. Anesthesiology 130 9952163
1993 Analysis of the sequence requirements for glycosylphosphatidylinositol anchoring of Saccharomyces cerevisiae Gas1 protein. The Journal of biological chemistry 119 8486709
2007 Gas1 is a modifier for holoprosencephaly and genetically interacts with sonic hedgehog. The Journal of clinical investigation 116 17525797
2008 A genome-wide shRNA screen identifies GAS1 as a novel melanoma metastasis suppressor gene. Genes & development 102 18981472
2013 MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway. Biochemical and biophysical research communications 98 24220341
1996 Evidence for two tumor suppressor loci associated with proximal chromosome 9p to q and distal chromosome 9q in bladder cancer and the initial screening for GAS1 and PTC mutations. Cancer research 96 8895761
1995 Gas1-induced growth suppression requires a transactivation-independent p53 function. Molecular and cellular biology 96 8524283
1997 A proline-rich motif in p53 is required for transactivation-independent growth arrest as induced by Gas1. Proceedings of the National Academy of Sciences of the United States of America 83 9114050
1997 Myc represses transcription of the growth arrest gene gas1. Proceedings of the National Academy of Sciences of the United States of America 79 9371770
2000 Chitin synthesis in a gas1 mutant of Saccharomyces cerevisiae. Journal of bacteriology 74 10940014
1994 Structure, function, and chromosome mapping of the growth-suppressing human homologue of the murine gas1 gene. Proceedings of the National Academy of Sciences of the United States of America 74 8127893
2020 NOTCH4 maintains quiescent mesenchymal-like breast cancer stem cells via transcriptionally activating SLUG and GAS1 in triple-negative breast cancer. Theranostics 70 32104513
2014 Down-regulation of miR-34a alleviates mesangial proliferation in vitro and glomerular hypertrophy in early diabetic nephropathy mice by targeting GAS1. Journal of diabetes and its complications 62 24560136
2003 Gas1 is induced by VE-cadherin and vascular endothelial growth factor and inhibits endothelial cell apoptosis. Blood 62 15070677
2000 The growth suppressing gas1 product is a GPI-linked protein. FEBS letters 61 10996315
2016 Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma. Molecular cancer research : MCR 55 27401611
2006 Gas1 is related to the glial cell-derived neurotrophic factor family receptors alpha and regulates Ret signaling. The Journal of biological chemistry 55 16551639
2005 Fusarium oxysporum gas1 encodes a putative beta-1,3-glucanosyltransferase required for virulence on tomato plants. Molecular plant-microbe interactions : MPMI 55 16353549
2007 The role of Gas1 in embryonic development and its implications for human disease. Cell cycle (Georgetown, Tex.) 54 17726382
2023 Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1. Cancer communications (London, England) 52 37533188
2006 Is GAS1 a co-receptor for the GDNF family of ligands? Trends in pharmacological sciences 51 16406089
2005 Effect of oxidative stress on translocation of DAF-16 in oxygen-sensitive mutants, mev-1 and gas-1 of Caenorhabditis elegans. Mechanisms of ageing and development 49 15888316
2011 Contribution of the gas1 gene of the entomopathogenic fungus Beauveria bassiana, encoding a putative glycosylphosphatidylinositol-anchored beta-1,3-glucanosyltransferase, to conidial thermotolerance and virulence. Applied and environmental microbiology 48 21357429
2011 Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH. Human genetics 48 21842183
2010 Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients. American journal of medical genetics. Part A 46 20583177
1998 Tumor-suppressive activity of the growth arrest-specific gene GAS1 in human tumor cell lines. International journal of cancer 46 9466658
1998 Growth-regulatory activity of the growth arrest-specific gene, GAS1, in NIH3T3 fibroblasts. Experimental cell research 45 9597009
2008 O-mannosylation is required for degradation of the endoplasmic reticulum-associated degradation substrate Gas1*p via the ubiquitin/proteasome pathway in Saccharomyces cerevisiae. Journal of biochemistry 44 18182384
2015 WT1 targets Gas1 to maintain nephron progenitor cells by modulating FGF signals. Development (Cambridge, England) 43 25804736
2012 GAS1 induces cell death through an intrinsic apoptotic pathway. Apoptosis : an international journal on programmed cell death 43 22311470
2004 Characterization of recombinant forms of the yeast Gas1 protein and identification of residues essential for glucanosyltransferase activity and folding. European journal of biochemistry 43 15355340
2002 Maintenance of cell integrity in the gas1 mutant of Saccharomyces cerevisiae requires the Chs3p-targeting and activation pathway and involves an unusual Chs3p localization. Yeast (Chichester, England) 41 12237852
2014 Gas1 is a receptor for sonic hedgehog to repel enteric axons. Proceedings of the National Academy of Sciences of the United States of America 40 25535338
2009 Identification of GAS1 as an epirubicin resistance-related gene in human gastric cancer cells with a partially randomized small interfering RNA library. The Journal of biological chemistry 39 19638344
2008 Gas1 reduces Ret tyrosine 1062 phosphorylation and alters GDNF-mediated intracellular signaling. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 39 18394855
2009 Immobilization of the glycosylphosphatidylinositol-anchored Gas1 protein into the chitin ring and septum is required for proper morphogenesis in yeast. Molecular biology of the cell 38 19793924
1996 Candida albicans homologue of GGP1/GAS1 gene is functional in Saccharomyces cerevisiae and contains the determinants for glycosylphosphatidylinositol attachment. Yeast (Chichester, England) 38 8701608
2002 Gas1 is induced during and participates in excitotoxic neuronal death. Molecular and cellular neurosciences 36 11906213
2001 Embryonic expression patterns of the mouse and chick Gas1 genes. Mechanisms of development 36 11231094
2003 Transcriptionally mediated gene targeting of gas1 to glioma cells elicits growth arrest and apoptosis. Journal of neuroscience research 35 12503088
2009 Gas1 inhibits cell proliferation and induces apoptosis of human primary gliomas in the absence of Shh. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 34 19460624
2006 Cloning, disruption and protein secretory phenotype of the GAS1 homologue of Pichia pastoris. FEMS microbiology letters 33 17020547
2020 Parkin ubiquitinates GATA4 and attenuates the GATA4/GAS1 signaling and detrimental effects on diabetic nephropathy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 32436607
2009 The glucanosyltransferase Gas1 functions in transcriptional silencing. Proceedings of the National Academy of Sciences of the United States of America 32 19541632
2000 Analysis of the domain requirement in Gas1 growth suppressing activity. FEBS letters 32 10996316
2013 Succinate dehydrogenase upregulation destabilize complex I and limits the lifespan of gas-1 mutant. PloS one 31 23555681
2014 A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model. Experimental cell research 30 24992044
2000 Improved secretion of native human insulin-like growth factor 1 from gas1 mutant Saccharomyces cerevisiae cells. Applied and environmental microbiology 30 11097931
2012 Gastrointestinal defects of the Gas1 mutant involve dysregulated Hedgehog and Ret signaling. Biology open 29 23429478
2011 Gas1 cooperates with Cdo and promotes myogenic differentiation via activation of p38MAPK. Cellular signalling 29 21820049
2010 Down-regulated GAS1 expression correlates with recurrence in stage II and III colorectal cancer. Human pathology 29 21111449
2019 Muscle stem cell renewal suppressed by Gas1 can be reversed by GDNF in mice. Nature metabolism 27 32021964
2014 Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function. Biology open 26 25063195
2016 MiR-184 Regulates Proliferation in Nucleus Pulposus Cells by Targeting GAS1. World neurosurgery 25 26805687
2014 Neural stem cells producing an inducible and soluble form of Gas1 target and inhibit intracranial glioma growth. Cytotherapy 25 24529556
2007 Targeted-simultaneous expression of Gas1 and p53 using a bicistronic adenoviral vector in gliomas. Cancer gene therapy 24 17599090
2007 Hedgehog signaling: cooking with Gas1. Science's STKE : signal transduction knowledge environment 24 17848687
2020 Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration. Nature communications 22 32332736
2016 Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. Journal of neuroinflammation 22 27391369
2010 Lentiviral transfer of an inducible transgene expressing a soluble form of Gas1 causes glioma cell arrest, apoptosis and inhibits tumor growth. Cancer gene therapy 22 20885451
2000 Increase of external osmolarity reduces morphogenetic defects and accumulation of chitin in a gas1 mutant of Saccharomyces cerevisiae. Journal of bacteriology 21 10648547
2019 gas1 mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in Schizosaccharomyces pombe. Bioscience, biotechnology, and biochemistry 19 31601154
2016 Growth Arrest Specific-1 (GAS1) Is a C/EBP Target Gene That Functions in Ovulation and Corpus Luteum Formation in Mice. Biology of reproduction 19 26740594
2016 WT1 is involved in the Akt-JNK pathway dependent autophagy through directly regulating Gas1 expression in human osteosarcoma cells. Biochemical and biophysical research communications 19 27453337
2009 A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1. The Journal of biological chemistry 19 19478089
2014 The β-1,3-glucanosyltransferase Gas1 regulates Sir2-mediated rDNA stability in Saccharomyces cerevisiae. Nucleic acids research 18 24981510
2014 Gas1 is a pleiotropic regulator of cellular functions: from embryonic development to molecular actions in cancer gene therapy. Mini reviews in medicinal chemistry 18 25429664
2018 Additive effects of the combined expression of soluble forms of GAS1 and PTEN inhibiting glioblastoma growth. Gene therapy 17 29941984
2010 Cloning of the Zygosaccharomyces bailii GAS1 homologue and effect of cell wall engineering on protein secretory phenotype. Microbial cell factories 17 20102600
2016 Paths of Heritable Mitochondrial DNA Mutation and Heteroplasmy in Reference and gas-1 Strains of Caenorhabditis elegans. Frontiers in genetics 16 27148352
1998 Role of Gas1 down-regulation in mitogenic stimulation of quiescent NIH3T3 cells by v-Src. Oncogene 16 9796692
2023 Loss of ATOH1 in Pit Cell Drives Stemness and Progression of Gastric Adenocarcinoma by Activating AKT/mTOR Signaling through GAS1. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 37824217
2021 Gas1 Regulates Patterning of the Murine and Human Dentitions through Sonic Hedgehog. Journal of dental research 15 34796774
2020 Desert Hedgehog-Driven Endothelium Integrity Is Enhanced by Gas1 (Growth Arrest-Specific 1) but Negatively Regulated by Cdon (Cell Adhesion Molecule-Related/Downregulated by Oncogenes). Arteriosclerosis, thrombosis, and vascular biology 15 33028094
2018 Microglia induces Gas1 expression in human brain tumor-initiating cells to reduce tumorigenecity. Scientific reports 15 30327548
1997 Fine mapping of the hereditary sensory neuropathy type I locus on chromosome 9q22.1-->q22.3: exclusion of GAS1 and XPA. Cytogenetics and cell genetics 15 9371409
2023 GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure. International journal of medical sciences 13 37859699
2011 Epigenetic transcriptional regulation of the growth arrest-specific gene 1 (Gas1) in hepatic cell proliferation at mononucleosomal resolution. PloS one 13 21858068
1995 The human growth-arrest-specific gene GAS1 maps outside the candidate region of the gene for nevoid basal cell carcinoma syndrome. Cytogenetics and cell genetics 13 7956349
2021 GAS1: A New β-Glucan Immunostimulant Candidate to Increase Rainbow Trout (Oncorhynchus mykiss) Resistance to Bacterial Infections With Aeromonas salmonicida achromogenes. Frontiers in immunology 12 34295335
2017 Gas1 expression in parietal cells of Bowman's capsule in experimental diabetic nephropathy. Histochemistry and cell biology 12 28315934
2017 Downregulation of OCLN and GAS1 in clear cell renal cell carcinoma. Oncology reports 11 28184927
2017 Evaluation of Saccharomyces cerevisiae GAS1 with respect to its involvement in tolerance to low pH and salt stress. Journal of bioscience and bioengineering 11 28476241
2005 Three-dimensional structure of the catalytic domain of the yeast beta-(1,3)-glucan transferase Gas1: a molecular modeling investigation. Journal of molecular modeling 11 16240096
1993 Estrogen-regulated expression of a growth arrest specific gene (gas-1) in rat uterus. Cell biology international 11 8220312
2017 Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1-induced cell cycle arrest. Journal of cellular physiology 10 29030970
2014 Unexpected function of the glucanosyltransferase Gas1 in the DNA damage response linked to histone H3 acetyltransferases in Saccharomyces cerevisiae. Genetics 10 24532730
2013 Growth arrest specific 1 (GAS1) is abundantly expressed in the adult mouse central nervous system. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 10 23813868
1993 Structure and regulation of the growth arrest-specific (gas-1) promoter. The Journal of biological chemistry 10 8226788
2021 GAS1 is required for NOTCH-dependent facilitation of SHH signaling in the ventral forebrain neuroepithelium. Development (Cambridge, England) 9 34698766
2016 GAS1 is present in the cerebrospinal fluid and is expressed in the choroid plexus of the adult rat. Histochemistry and cell biology 9 27225491
2015 Gas1 is present in germinal niches of developing dentate gyrus and cortex. Cell and tissue research 9 26714727

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