Affinage

GAS1

Growth arrest-specific protein 1 · UniProt P54826

Length
345 aa
Mass
35.7 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GAS1 is a GPI-anchored plasma membrane glycoprotein that functions as a multivalent co-receptor integrating Hedgehog signaling and growth factor receptor tyrosine kinase signaling to regulate cell proliferation, differentiation, and survival. As a Hedgehog pathway co-receptor, GAS1 binds Sonic Hedgehog on a surface distinct from the Ptch1-binding site and cooperates with Ptch1, CDO, and BOC to potentiate Hh signaling in a cell-autonomous manner; compound loss of all three co-receptors abolishes Hh pathway activity, and GAS1 patient variants that reduce SHH binding are associated with holoprosencephaly (PMID:17504941, PMID:21664576, PMID:21842183). Independently of Hedgehog signaling, GAS1 binds the RET receptor tyrosine kinase in a ligand-independent manner, sequesters it in lipid rafts, blocks Ret Tyr1062 phosphorylation, and suppresses downstream Akt signaling, thereby triggering intrinsic apoptosis through BAD dephosphorylation, cytochrome-c release, and caspase-9/3 activation (PMID:16551639, PMID:22311470, PMID:37824217). GAS1-mediated growth suppression requires a transactivation-independent p53 function mediated through the p53 proline-rich region, and GAS1 expression is transcriptionally controlled by c-Myc (repression), WT1, NOTCH4, ATOH1, and FOXM1 (PMID:8524283, PMID:9114050, PMID:9371770, PMID:25804736).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1992 High

    The fundamental question of whether GAS1 is merely a growth-arrest marker or an active growth suppressor was resolved: overexpression blocks the G0-to-S transition and DNA synthesis, establishing GAS1 as a functional negative regulator of cell proliferation.

    Evidence Overexpression via constitutive promoter and microinjection in normal and transformed NIH 3T3 cells with DNA synthesis assay

    PMID:1505026

    Open questions at the time
    • Mechanism of growth suppression unknown
    • Receptor or signaling pathway not identified
    • Endogenous loss-of-function not tested
  2. 1997 High

    The downstream effector pathway was identified: GAS1-mediated growth arrest requires p53 but operates through a transactivation-independent mechanism dependent on the p53 proline-rich region (aa 63–85), distinguishing it from canonical p53 transcriptional programs.

    Evidence Overexpression of GAS1 in p53-null and p53-mutant cells; deletion and site-directed mutagenesis of p53 proline-rich domain with functional rescue

    PMID:8524283 PMID:9114050

    Open questions at the time
    • Direct physical interaction between GAS1 and p53 not demonstrated
    • Identity of the p53-dependent downstream target unknown
    • Mechanism by which GAS1 activates the p53 proline-rich domain pathway unresolved
  3. 1997 High

    Transcriptional regulation of GAS1 was placed in the oncogenic network: c-Myc represses gas1 via Myc box 2, and this repression is required for Myc-driven proliferation and transformation.

    Evidence Promoter-reporter assays with Myc box 2 mutants, inducible Myc-ER fusion system, transformation assays

    PMID:9371770

    Open questions at the time
    • Whether Myc binds the gas1 promoter directly or indirectly not determined
    • Relevance to in vivo tumorigenesis not tested
  4. 2000 High

    The membrane topology and post-translational processing of GAS1 were defined: it is a GPI-anchored, N-glycosylated protein on the outer plasma membrane leaflet that relocalizes to caveolae upon clustering, and the GPI anchor is dispensable for growth suppression.

    Evidence In vitro translation, immunoelectron microscopy, subcellular fractionation, GPI-anchor-deficient mutant proliferation assay

    PMID:10996315 PMID:10996316

    Open questions at the time
    • Functional significance of caveolar relocalization unclear
    • Identity of extracellular domains required for growth suppression not mapped at residue level
  5. 2003 High

    GAS1 was connected to two additional biological contexts—excitotoxic neuronal death and endothelial survival—revealing that its pro- or anti-apoptotic function is context-dependent: GAS1 induces intrinsic apoptosis in neurons but mediates VEGF-dependent anti-apoptosis in endothelial cells.

    Evidence Gas1 overexpression/knockdown in hippocampal neurons with Bcl-2 rescue; siRNA knockdown in endothelial cells with PI3K inhibition and VE-cadherin clustering assay

    PMID:11906213 PMID:15070677

    Open questions at the time
    • Molecular basis for context-dependent pro- vs anti-apoptotic switching not identified
    • Neuronal co-IP partner OpIAP2 not validated with reciprocal IP or in vivo
  6. 2006 High

    A major new signaling axis was uncovered: GAS1 shares structural homology with GFRα receptors, physically binds Ret in a ligand-independent manner, sequesters Ret in lipid rafts, and blocks Akt activation, explaining how GAS1 opposes GDNF-dependent survival.

    Evidence Structural bioinformatics, reciprocal co-immunoprecipitation, lipid raft fractionation, pAkt and pERK signaling assays

    PMID:16551639

    Open questions at the time
    • Structure of the GAS1-Ret complex not determined
    • Whether GAS1 competes with GFRα for Ret binding not resolved
  7. 2007 High

    GAS1 was established as a bona fide Hedgehog co-receptor: it binds SHH, cooperates with Ptch1 and CDO, and is genetically required for Shh-dependent ventral neural tube patterning, extending the effective range of Hh signaling especially at low ligand concentrations.

    Evidence Gas1 knockout mice, in ovo electroporation, cell surface binding assays, compound Gas1/Cdo mutant analysis

    PMID:17504940 PMID:17504941

    Open questions at the time
    • Structural basis of GAS1-SHH binding unknown
    • Relative contributions of GAS1 vs CDO vs BOC across tissues not delineated
  8. 2009 High

    The molecular interface between SHH and GAS1 was partially defined: SHH harbors a unique GAS1-binding surface distinct from its Ptch1-binding site, and the HPE-associated SHH-N115K mutation selectively disrupts GAS1 binding, providing a mechanistic link to holoprosencephaly.

    Evidence Cell surface binding assay with SHH point mutants, explant culture activity assay

    PMID:19478089

    Open questions at the time
    • Atomic-resolution structure of the GAS1-SHH complex not available
    • Whether additional SHH residues contribute to GAS1 binding not exhaustively mapped
  9. 2011 High

    The co-receptor requirement was shown to be obligatory and collectively essential: triple knockout of Gas1, Cdo, and Boc completely abolishes Hh pathway activity across multiple tissues, and GAS1 patient variants with reduced SHH affinity directly link GAS1 to holoprosencephaly.

    Evidence Single, double, and triple genetic knockouts in mice; cell surface binding assay with GAS1 HPE patient missense variants

    PMID:21664576 PMID:21664577 PMID:21842183

    Open questions at the time
    • Mechanism by which co-receptor binding is transduced to Smo de-repression not defined
    • Tissue-specific contributions of each co-receptor incompletely mapped
  10. 2012 High

    The apoptotic mechanism downstream of GAS1-Ret was fully delineated: GAS1 suppresses Ret Tyr1062 phosphorylation, inhibits Akt, dephosphorylates BAD, triggers cytochrome-c release, and activates caspase-9/3 but not caspase-8, confirming an intrinsic mitochondrial apoptotic pathway.

    Evidence Caspase activity assays, cytochrome-c release assay, phospho-Akt and phospho-BAD western blot, Gas1 siRNA knockdown

    PMID:22311470

    Open questions at the time
    • Whether GAS1-induced apoptosis operates identically in non-neuronal cell types not established
    • Direct structural basis for Ret Y1062 dephosphorylation unknown
  11. 2014 High

    GAS1's role in Hh signaling was extended to axon guidance: in enteric neurons, GAS1 mediates Shh-dependent axon repulsion through Smoothened and the downstream effector Gαz (Gnaz), revealing a non-canonical Hh output.

    Evidence In vitro enteric neuron axon turning assay, Gas1 knockout, Gnaz knockdown and dominant-negative, Gnaz mutant intestine

    PMID:25535338

    Open questions at the time
    • Whether Gαz-dependent axon repulsion operates outside the enteric nervous system unknown
    • How GAS1-Smo coupling activates Gαz not resolved
  12. 2015 High

    WT1 was identified as a direct transcriptional activator of Gas1 in nephron progenitor cells, placing Gas1 in the WT1-FGF-AKT signaling circuit required for nephron progenitor maintenance.

    Evidence ChIP of WT1 at Gas1 promoter, Gas1 knockout mice, FGF-AKT signaling assay in nephron progenitors

    PMID:25804736

    Open questions at the time
    • Whether Gas1 in this context signals via Ret or Hh pathway not determined
    • Role of Gas1 in later stages of nephrogenesis not explored
  13. 2019 High

    The GAS1-Ret axis was shown to regulate muscle stem cell quiescence and self-renewal: Gas1 suppresses Ret signaling in MuSCs, and GDNF counteracts Gas1 to promote Ret-dependent self-renewal and muscle regeneration.

    Evidence Gas1 overexpression and conditional knockout in MuSCs, Ret signaling assays, in vivo muscle regeneration

    PMID:32021964

    Open questions at the time
    • Mechanism of Gas1 downregulation during MuSC activation not defined
    • Whether Gas1-Ret interaction in MuSCs involves lipid raft sequestration not tested
  14. 2020 Medium

    The Hedgehog co-receptor role was refined: Gas1 forms a distinct complex with Ptch2 (not only Ptch1) to mediate non-canonical Hh signaling through pCreb and pSrc, and in endothelial cells Gas1 potentiates Desert Hedgehog signaling to maintain vascular quiescence.

    Evidence Compound mutant mice for primordial germ cell migration; EC-specific conditional Gas1 knockout with Dhh binding assays and VCAM-1/ICAM-1 quantification

    PMID:32332736 PMID:33028094

    Open questions at the time
    • Structural basis for Ptch2-Gas1 versus Ptch1-Gas1 selectivity unknown
    • Whether pCreb/pSrc non-canonical arm operates in other Hh-responsive tissues not tested
  15. 2023 High

    The GAS1-RET inhibitory axis was validated in cancer: ATOH1 transcriptionally activates GAS1, which complexes with RET to block Tyr1062 phosphorylation; loss of this circuit activates RET/AKT/mTOR to drive cancer stemness and chemoresistance in gastric adenocarcinoma.

    Evidence ChIP of ATOH1 at GAS1 promoter, co-IP of GAS1-RET, phospho-RET Y1062 western blot, organoid models with GAS1 overexpression/knockdown

    PMID:37824217

    Open questions at the time
    • Whether GAS1-RET stoichiometry determines signaling output not known
    • Therapeutic potential of restoring GAS1 expression not evaluated in preclinical models

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of GAS1's simultaneous engagement with SHH and RET; how GAS1 switches between pro-apoptotic and anti-apoptotic functions in different cellular contexts; and the mechanism by which co-receptor binding to Hh is transduced to Smoothened de-repression.
  • No atomic-resolution structure of GAS1 in complex with SHH or RET
  • Molecular basis for context-dependent pro- vs anti-apoptotic switching unresolved
  • Signal transduction from co-receptor-Hh binding to Smo de-repression mechanistically undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0060090 molecular adaptor activity 4
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 4 R-HSA-5357801 Programmed Cell Death 2
Partners
BOCCDOPTCH1PTCH2RETSHH

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 GAS1 encodes an integral plasma membrane protein whose overexpression from a constitutive promoter inhibits the G0-to-S phase transition in serum-stimulated quiescent cells and blocks DNA synthesis in normal and transformed NIH 3T3 cells, except SV40-transformed cells, identifying it as a component of a negative growth-suppression circuit. Overexpression by constitutive promoter, microinjection, DNA synthesis assay Cell High 1505026
1995 Gas1-induced growth suppression requires p53 function but is independent of p53's N-terminal transactivation domain, indicating Gas1 activates a transactivation-independent p53 pathway to block the G0-to-S transition. Overexpression of Gas1 in p53-null and p53-mutant cells, cell cycle analysis Molecular and cellular biology High 8524283
1997 The proline-rich region (amino acids 63–85) of p53 is required for Gas1-dependent transactivation-independent growth arrest, as shown by deletion analysis and site-specific mutagenesis of p53, identifying this domain as a docking site for Gas1 antiproliferative signaling. Deletion analysis, site-directed 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 gene expression via Myc box 2, and repression of gas1 is required for Myc-driven cell proliferation and transformation but not for ODC activation. Promoter-reporter assays, Myc mutant analysis (Myc-ER fusion activated by 4-OHT), transformation assays Proceedings of the National Academy of Sciences of the United States of America High 9371770
2000 Gas1 is a GPI-anchored protein that undergoes cotranslational signal peptide cleavage, N-linked glycosylation, and GPI anchor addition in the ER; in mature form it is randomly distributed on the outer leaflet of the plasma membrane and, upon antibody-induced clustering, relocalizes to caveolae. In vitro translation, immunofluorescence, immunoelectron microscopy, subcellular fractionation FEBS letters High 10996315
2000 The GPI anchor of Gas1 is dispensable for its growth suppression function, and specific extracellular domains of Gas1 are required for its antiproliferative activity. Domain deletion analysis, GPI-anchor-deficient mutants, cell proliferation assay FEBS letters Medium 10996316
2006 Gas1 shows structural homology to GFRα receptors, binds the Ret receptor tyrosine kinase in a ligand-independent manner, sequesters Ret in lipid rafts, and modifies downstream Ret signaling through Shc and ERK, ultimately blocking Akt activation and compromising GDNF-dependent neuronal survival. Structural bioinformatics, co-immunoprecipitation, lipid raft fractionation, signaling assays (pAkt, pERK) The Journal of biological chemistry High 16551639
2007 Gas1 binds Sonic Hedgehog (Shh) and acts cooperatively with Patched1 (Ptch1) for Shh binding, enhancing Shh signaling activity in a cell-autonomous fashion; genetic loss of Gas1 causes Shh dose-dependent loss of ventral neural tube cell identities, and ectopic Gas1 expression promotes ventral cell fates in a Shh-dependent manner. Genetic loss-of-function (Gas1 knockout mice), ectopic expression (in ovo electroporation), in vitro cell surface binding assay, neural tube patterning assay Genes & development High 17504940 17504941
2007 Gas1 extends the effective range of Hedgehog signaling particularly at low Hh concentrations by acting cooperatively with Ptch1 for Hh binding in a cell-autonomous manner, converting the Hh protein concentration gradient into the activity gradient. In vitro cell culture binding assays, in ovo electroporation, genetic loss-of-function analysis Genes & development High 17504940
2007 GAS1 and CDO (Cdo) cooperate to promote Shh signaling during neural tube patterning, craniofacial, and vertebral development; both Gas1 and Cdo encode cell-surface Shh-binding proteins, and Gas1 expression is negatively regulated by active Hh signaling. Double-mutant genetic analysis (Gas1/Cdo compound knockouts), neural tube patterning assays Genes & development High 17504941
2008 Gas1 reduces GDNF-induced phosphorylation of Ret tyrosine 1062 and significantly decreases Akt activation in neuroblastoma cells, defining Gas1 as a negative modulator of GDNF-Ret intracellular survival signaling. Phospho-specific western blot (pRet Y1062, pAkt), Gas1 overexpression in SH-SY5Y cells International journal of developmental neuroscience Medium 18394855
2009 SHH contains a unique binding surface for GAS1 distinct from its Ptch1-binding surface; the HPE-associated missense mutation SHH-N115K severely reduces SHH binding to GAS1, providing a mechanistic basis for HPE pathogenesis via impaired GAS1-SHH interaction. Cell surface binding assay, in vitro activity assay, explant culture assay, mutagenesis The Journal of biological chemistry High 19478089
2011 GAS1, CDO, and BOC play overlapping and collectively essential roles as Hh coreceptors during ventral neural tube patterning; genetic loss of all three abolishes HH pathway activity in multiple tissues, demonstrating an obligatory requirement for these coreceptors. Single and compound genetic knockouts (Gas1, Cdo, Boc mutant mice), neural tube patterning and cell fate assays Developmental cell High 21664576 21664577
2011 Boc and Gas1 each form distinct receptor complexes with Ptch1; Gas1 mediates Hh-dependent cerebellar granule neuron progenitor proliferation in the absence of Boc and Cdon, and only loss of all three molecules (Boc, Cdon, Gas1) completely abolishes Hh-dependent proliferation. Genetic loss-of-function (triple knockout), CGNP proliferation assay, Hh ligand binding mutants Developmental cell High 21664577
2011 Missense variants in GAS1 found in holoprosencephaly patients reduce the binding affinity of GAS1 for its ligand SHH, mechanistically linking GAS1 coding variants to impaired SHH signaling in HPE. Cell surface binding assay with SHH, site-directed mutagenesis of GAS1 patient variants Human genetics High 21842183
2011 Gas1 and Cdo are co-expressed in muscle cells, form a protein complex in differentiating myoblasts, and Gas1 promotes myogenic differentiation by facilitating p38MAPK activation downstream of Cdo and by regulating cell cycle exit (downregulation of Cdk2 and Cyclin D1, upregulation of miR-322). Co-immunoprecipitation, Gas1 overexpression and knockdown, p38MAPK signaling assays, myogenic differentiation markers Cellular signalling Medium 21820049
2012 Gas1 induces apoptosis via an intrinsic pathway by reducing Ret phosphorylation, inhibiting Akt activation, triggering BAD dephosphorylation, releasing cytochrome-c from mitochondria, and activating caspase-9 and caspase-3; caspase-8 is not activated, confirming intrinsic (not extrinsic) apoptosis. Caspase activity assays, cytochrome-c release, western blotting (pAkt, pBAD), caspase-8 exclusion assay, siRNA knockdown of Gas1 Apoptosis High 22311470
2014 Gas1 acts as a receptor for Sonic hedgehog (Shh) in enteric neurons to mediate axon repulsion; Shh presented as a point source causes enteric axons to turn away in a Gas1-dependent manner requiring Smoothened (Smo) and Gαz (Gnaz) as an effector coupling Smo to axon guidance. In vitro enteric neuron axon turning assay, Gas1 knockout, Gnaz knockdown and dominant negative, Gnaz mutant intestine analysis Proceedings of the National Academy of Sciences of the United States of America High 25535338
2015 WT1 directly binds a conserved motif in the Gas1 promoter and activates Gas1 transcription in nephron progenitor cells; WT1-mediated Gas1 expression is required for FGF-stimulated AKT signaling and nephron progenitor maintenance in vivo. Chromatin immunoprecipitation (ChIP) of WT1 at Gas1 promoter, Gas1 knockout mice, FGF-AKT signaling assay Development (Cambridge, England) High 25804736
2019 Gas1 is expressed in muscle stem cells (MuSCs) and suppresses Ret signaling required for MuSC quiescence and self-renewal; GDNF counteracts Gas1 by stimulating Ret signaling and enhancing MuSC self-renewal and muscle regeneration. Gas1 overexpression and conditional knockout in MuSCs, Ret signaling assays, muscle regeneration assays Nature metabolism High 32021964
2020 In endothelial cells, Gas1 promotes Desert Hedgehog (Dhh) binding to Smo and potentiates Dhh signaling, while Cdon acts as a decoy receptor preventing Dhh binding to Ptch1; Gas1 deficiency phenocopies Dhh deficiency inducing VCAM-1 and ICAM-1 overexpression. siRNA knockdown, EC-specific conditional knockout mice, Dhh-Ptch1-Smo binding assays, inflammatory marker quantification Arteriosclerosis, thrombosis, and vascular biology Medium 33028094
2020 Ptch2/Gas1 and Ptch1/Boc form distinct hetero-receptor complexes that mediate Smo de-repression with different kinetics; Ptch2-Gas1 signaling induces phosphorylation of Creb and Src in addition to Gli, identifying a Ptch2-specific non-canonical Hedgehog signal pathway. Primordial germ cell migration assay in single and compound mutant mice, signaling pathway analysis (pCreb, pSrc, Gli) Nature communications Medium 32332736
2003 Gas1 is induced in neurons undergoing NMDA-induced excitotoxic death, and overexpression of Gas1 in hippocampal neurons induces apoptosis; baculoviral caspase inhibitor OpIAP2 co-immunoprecipitates with Gas1, and Gas1-induced neuronal death is attenuated by Bcl-2 or OpIAP2 co-expression. Co-immunoprecipitation (Gas1-OpIAP2), overexpression, antisense oligodeoxynucleotide knockdown, Bcl-2 rescue Molecular and cellular neurosciences Medium 11906213
2003 VE-cadherin induces Gas1 expression in endothelial cells, and Gas1 mediates the antiapoptotic effect of VEGF; this induction requires PI3-kinase activity and VE-cadherin clustering, and siRNA knockdown of Gas1 makes endothelial cells refractory to VEGF-mediated antiapoptosis. siRNA knockdown, ectopic Gas1 expression, PI3K inhibitor (Wortmannin), allantois organ culture, VE-cadherin blocking antibody Blood High 15070677
2014 A soluble form of GAS1 (tGAS1) inhibits breast cancer cell growth and tumor angiogenesis via a RET-independent mechanism involving inhibition of Artemin (ARTN)-GFRα3-ERK signaling, and prevents endothelial cell migration. In vitro viability assay, in vivo tumor implantation, endothelial migration assay, ERK signaling assay, RET-independent binding assay Experimental cell research Medium 24992044
2016 Gas1 inhibits aerobic glycolysis (Warburg effect) in colorectal cancer cells by decreasing expression of glycolytic enzymes (GLUT4, HK2, LDHB) and negatively regulating the AMPK/mTOR/p70S6K signaling axis; Gas1 is itself a transcriptional target of FOXM1. Gas1 knockdown/overexpression, glycolysis metabolic assays, 18FDG-PET/CT in vivo, signaling pathway western blot, FOXM1 ChIP Molecular cancer research Medium 27401611
2020 NOTCH4 transcriptionally upregulates GAS1 by directly binding to the GAS1 promoter, promoting quiescence of mesenchymal-like breast cancer stem cells (ML-BCSCs); SLUG (downstream of NOTCH4) also harnasses GAS1 via its anti-apoptotic function. Dual-luciferase reporter assay, chromatin immunoprecipitation (ChIP) of NOTCH4 at GAS1 promoter, RNA-seq, stable overexpression/knockdown Theranostics Medium 32104513
2020 Parkin (E3-ubiquitin ligase) directly interacts with GATA4 and promotes its ubiquitination, leading to downregulation of GAS1 expression; GATA4 overexpression enhances GAS1 transcription and GAS1 overexpression mediates renal tubular cell senescence, inflammation and fibrosis in diabetic nephropathy. Co-immunoprecipitation (Parkin-GATA4), ubiquitination assay, Parkin knockout/overexpression mice, GAS1 overexpression in RTECs FASEB journal Medium 32436607
2013 miR-34a directly targets the 3'-UTR of GAS1 mRNA to repress its expression in papillary thyroid carcinoma cells, and this regulation activates PI3K/Akt/Bad signaling to promote cell proliferation and suppress apoptosis. Luciferase 3'-UTR reporter assay, miR-34a overexpression/knockdown, GAS1 knockdown, Akt inhibition rescue Biochemical and biophysical research communications Medium 24220341
2017 Annexin A1, Annexin A2, and Dyrk1B are upregulated at both transcriptional and translational levels by GAS1 overexpression during cell cycle arrest; Dyrk1B upregulation by GAS1 contributes to cell arrest while maintaining cell viability in NIH3T3 cells. 2D-gel proteomics, mass spectrometry, western blotting, transcriptional analysis, GAS1 overexpression Journal of cellular physiology Medium 29030970
2023 ATOH1 deficiency downregulates GAS1 by suppressing GAS1 promoter transcription; GAS1 forms a complex with RET and inhibits Tyr1062 phosphorylation of RET, so loss of GAS1 activates RET/AKT/mTOR signaling, promoting cancer stemness and chemoresistance in gastric adenocarcinoma. ChIP (ATOH1 at GAS1 promoter), co-immunoprecipitation (GAS1-RET complex), phospho-RET western blot, GAS1 knockdown/overexpression, organoid models Advanced science High 37824217

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 269 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 154 9878845
2001 Mitochondrial expression and function of GAS-1 in Caenorhabditis elegans. The Journal of biological chemistry 140 11278828
1999 GAS-1: a mitochondrial protein controls sensitivity to volatile anesthetics in the nematode Caenorhabditis elegans. Anesthesiology 127 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 112 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 69 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
2006 Is GAS1 a co-receptor for the GDNF family of ligands? Trends in pharmacological sciences 51 16406089
2023 Bifidobacterium adolescentis orchestrates CD143+ cancer-associated fibroblasts to suppress colorectal tumorigenesis by Wnt signaling-regulated GAS1. Cancer communications (London, England) 49 37533188
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 42 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
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
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 31 32436607
2014 A soluble form of GAS1 inhibits tumor growth and angiogenesis in a triple negative breast cancer model. Experimental cell research 30 24992044
2013 Succinate dehydrogenase upregulation destabilize complex I and limits the lifespan of gas-1 mutant. PloS one 30 23555681
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 26 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
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
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 21 27391369
2000 Increase of external osmolarity reduces morphogenetic defects and accumulation of chitin in a gas1 mutant of Saccharomyces cerevisiae. Journal of bacteriology 21 10648547
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
2019 gas1 mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in Schizosaccharomyces pombe. Bioscience, biotechnology, and biochemistry 18 31601154
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
1998 Role of Gas1 down-regulation in mitogenic stimulation of quiescent NIH3T3 cells by v-Src. Oncogene 16 9796692
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
2016 Paths of Heritable Mitochondrial DNA Mutation and Heteroplasmy in Reference and gas-1 Strains of Caenorhabditis elegans. Frontiers in genetics 15 27148352
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 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) 14 37824217
1995 Isolation and preliminary characterization of gas1-1, a mutation causing partial suppression of the phenotype conferred by the gibberellin-insensitive (gai) mutation in Arabidopsis thaliana (L.) Heyhn. Planta 14 8547820
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
2017 Gas1 expression in parietal cells of Bowman's capsule in experimental diabetic nephropathy. Histochemistry and cell biology 12 28315934
2023 GAS1 Promotes Ferroptosis of Liver Cells in Acetaminophen-Induced Acute Liver Failure. International journal of medical sciences 11 37859699
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 11 34295335
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 Downregulation of OCLN and GAS1 in clear cell renal cell carcinoma. Oncology reports 10 28184927
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
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