Affinage

Showing GOLM1 — GP73 is a alias.

GOLM1

Golgi membrane protein 1 · UniProt Q8NBJ4

Length
401 aa
Mass
45.3 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GOLM1 (GP73/GOLPH2) is a type II Golgi transmembrane glycoprotein that couples Golgi trafficking control to receptor signaling, secretion, and systemic metabolism, and is repeatedly co-opted to drive hepatocellular carcinoma and other cancers (PMID:10831838, PMID:27569582, PMID:25980751). Its Golgi residence is specified by the transmembrane domain plus a positively charged cytoplasmic residue, and the coiled-coil domain mediates disulfide-bonded dimerization and most protein-protein interactions (PMID:22140547). GOLM1 traffics from the cis-Golgi to the trans-Golgi network and endosomes, where furin-family proprotein convertases cleave a luminal consensus site to release a heavily fucosylated, N-glycosylated soluble ectodomain into serum (PMID:17662025, PMID:18004786). At the TGN, GOLM1 acts as a cargo adaptor that binds EGFR and other receptor tyrosine kinases to recycle them to the plasma membrane and prolong downstream kinase signaling, thereby promoting metastasis (PMID:27569582); a cholesterol-mTORC1 axis toggles this activity, since GOLM1 also engages LC3 through an LIR motif to route RTKs into selective autophagic degradation when cholesterol and mTORC1 are low (PMID:35443161). GOLM1 possesses TBC-domain Rab-GAP activity that controls hepatic ApoB export, and liver-specific overexpression drives non-obese NAFLD in a manner abolished by a GAP-inactive mutant and reversed by metformin (PMID:34853313). The secreted ectodomain functions as a fasting-induced glucogenic hormone that stimulates hepatic gluconeogenesis via cAMP/PKA signaling (PMID:34992299). GOLM1 additionally suppresses innate immunity by being recruited to MAVS via TRAF6 to drive proteasomal degradation of both, dampening IFN-β and NF-κB signaling (PMID:28394926), and promotes immune escape by stabilizing and exosomally exporting PD-L1 through EGFR/STAT3 (PMID:33294262, PMID:34795203). Across cancers GOLM1 is transcriptionally induced by c-Myc, ESE-1, TGF-β1, and IL-6/OSM-STAT3 signaling, and these inputs feed forward into PI3K-AKT-mTOR, EGFR, and STAT3 signaling axes (PMID:25530841, PMID:23144154, PMID:30615900, PMID:29181846, PMID:27569582).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 High

    Established the molecular identity and disease context of GP73: an integral Golgi membrane protein normally restricted from hepatocytes but induced by viral infection, framing it as a liver-disease-associated Golgi protein.

    Evidence In vitro transcription-translation, epitope-tag immunolocalization, Northern blot and IHC across epithelial tissues

    PMID:10831838

    Open questions at the time
    • No molecular function assigned
    • Mechanism of viral induction undefined
  2. 2002 High

    Defined how viral infection induces GP73, showing the adenoviral E1A CtBP-interaction domain is required, linking GP73 expression to a specific transcriptional co-repressor pathway.

    Evidence RNase protection, immunoblot/IF, and infection with E1A mutant adenoviruses plus transient E1A transfection

    PMID:12359426

    Open questions at the time
    • Did not map the cellular transcription factors recruited via CID
    • No endogenous viral context beyond adenovirus
  3. 2007 High

    Resolved the mechanism by which GP73 becomes a serum protein: furin-mediated cleavage at a PC consensus site in the endosomal compartment liberates the ectodomain, explaining its biomarker behavior.

    Evidence In vitro cleavage assay with purified furin, alanine mutagenesis of the cleavage site, cleavage-specific antibody and endosomal fractionation/IF

    PMID:17662025

    Open questions at the time
    • Function of the secreted ectodomain not yet known
    • Regulation of cleavage rate unaddressed
  4. 2008 High

    Characterized GP73 glycosylation (predominantly core-fucosylated bi-antennary structures) and showed the C-terminus is essential in vivo, with truncation causing kidney and liver pathology.

    Evidence Lectin chromatography/MS on recombinant and secreted GP73; gene-trap GP73^tr/tr mouse histopathology

    PMID:18004786 PMID:18830387

    Open questions at the time
    • Functional consequence of fucosylation undefined
    • Mechanism linking C-terminus to epithelial pathology unknown
  5. 2010 Medium

    Defined the structural determinants of GP73 — TM-plus-charged-residue Golgi targeting and coiled-coil-mediated dimerization — and identified secretory clusterin as an early binding partner.

    Evidence Truncation/domain-deletion mutants with IF localization and non-reducing SDS-PAGE; yeast two-hybrid, co-IP and co-localization for sCLU

    PMID:20842452 PMID:22140547

    Open questions at the time
    • sCLU interaction lacks functional/rescue validation
    • Functional role of dimerization untested
  6. 2012 Medium

    Connected GP73 expression to inflammatory cytokine signaling and defined core promoter architecture, showing IL-6/OSM-gp130-STAT3 induction and E1A/GC-box-mediated transactivation.

    Evidence Cytokine treatment of HepG2 with cycloheximide controls; promoter deletion/luciferase reporter assays with E1A mutants; Xenopus golph2 morpholino developmental study

    PMID:22542941 PMID:22719994 PMID:23144154

    Open questions at the time
    • Direct STAT3 binding to promoter not demonstrated
    • Vertebrate pronephros role mechanistically tied only to WT1 marker shifts
  7. 2014 Medium

    Identified direct transcription factors (ESE-1) and established a secretion-promoting role in HCV egress via the coiled-coil domain and ApoE interaction.

    Evidence ChIP and gain/loss-of-function for ESE-1; co-IP for GP73-ApoE plus stepwise HCV lifecycle assays with coiled-coil deletion

    PMID:24608522 PMID:25530841

    Open questions at the time
    • Whether GP73 acts as a general secretion adaptor beyond HCV unaddressed
    • Single-lab ChIP for ESE-1
  8. 2015 High

    Placed GOLM1 in a feed-forward oncogenic loop with mTORC1 and demonstrated causal tumor-promoting roles in HCC using KO, KD, OE, and xenograft models.

    Evidence GP73 KO mice, shRNA, retroviral OE, rapamycin treatment, xenografts and DEN-induced liver damage

    PMID:25980751

    Open questions at the time
    • Molecular effector of pro-tumor activity not yet defined at this stage
  9. 2016 High

    Defined GOLM1's signature molecular activity: a TGN cargo adaptor that binds EGFR/RTKs to recycle them to the plasma membrane and prolong kinase signaling; also linked Asn144 glycosylation to motility control.

    Evidence Reciprocal co-IP, RTK recycling assays, gain/loss-of-function in vivo; MS glycosite mapping with Asn144 mutagenesis and migration/invasion assays

    PMID:26993603 PMID:27569582

    Open questions at the time
    • How adaptor selectivity for RTKs is determined unclear
    • Glycosylation effect on adhesion partners not identified
  10. 2017 Medium

    Extended GOLM1 oncogenic signaling to PI3K-AKT-mTOR and PDGFA/PDGFRα-AKT cascades in prostate cancer and glioma, and identified MMP-7 trafficking under c-Myc/hypoxia control.

    Evidence Gain/loss-of-function with PI3K (BKM120), PDGFRα (AG1296) and AKT (MK-2206) inhibitors, kinase arrays, xenograft/orthotopic models; ChIP for c-Myc and co-IP for GP73-MMP-7

    PMID:29181846 PMID:29282077 PMID:31591387

    Open questions at the time
    • Whether AKT activation is direct or via RTK recycling not resolved
    • Single-lab studies per cancer type
  11. 2017 High

    Revealed an innate-immune-suppressive function: TRAF6-dependent recruitment of GP73 to MAVS drives proteasomal degradation of MAVS and TRAF6, attenuating antiviral signaling.

    Evidence Reciprocal co-IP, coiled-coil deletion mapping, proteasome inhibition, IFN-β/NF-κB reporters, knockdown+rescue in primary hepatocytes

    PMID:28394926

    Open questions at the time
    • Whether GP73 recruits an E3 ligase or acts directly is undefined
    • Generality beyond HCV-triggered signaling untested
  12. 2019 Medium

    Connected GOLM1 to TGF-β1 signaling rewiring and exosomal communication, showing it switches TGF-β1 from Smad to non-Smad (ERK/AKT) output and exports pro-tumor cargo via exosomes regulated by mTOR/miR-145.

    Evidence TGF-β1 reporter, lipid raft/caveolin-1 biochemistry, Smad/ERK/AKT phospho-blots; miR-145 luciferase CDS targeting and exosome transfer assays in vivo

    PMID:29365054 PMID:30615900 PMID:31186161

    Open questions at the time
    • Direct mechanism of Smad-to-nonSmad switch beyond lipid raft correlation unclear
    • Exosomal cargo selectivity undefined
  13. 2020 Medium

    Established GOLM1 as a driver of immune escape, upregulating and stabilizing PD-L1 via EGFR/STAT3 and routing PD-L1 into exosomes through CSN5 deubiquitination and Rab27b suppression.

    Evidence Gain/loss-of-function with STAT3 inhibition; ubiquitination assays, Rab27b analysis, exosome co-culture and CD8+ T cell flow cytometry; fibrosis transgenic models with EGFR inhibitors

    PMID:33294262 PMID:33992711 PMID:34795203

    Open questions at the time
    • Direct vs RTK-recycling-mediated EGFR effect not separated
    • Most readouts single-lab
  14. 2021 High

    Assigned GOLM1 an intrinsic enzymatic activity: TBC-domain Rab-GAP function controlling hepatocyte ApoB export and driving non-obese NAFLD, pharmacologically targetable by metformin.

    Evidence RabGAP activity assay, GAP-inactive TBC-domain mutant, liver-specific transgenic mice, ApoB export assays, metformin rescue

    PMID:34853313

    Open questions at the time
    • Specific Rab substrate(s) not definitively identified
    • Link between GAP activity and adaptor/autophagy roles unclear
  15. 2021 Medium

    Demonstrated developmental and homeostatic roles of GOLM1 in epithelium, p53 regulation, and AFP secretion, broadening its biology beyond signaling adaptor functions.

    Evidence GOLM1 KO mice colitis models with Notch (γ-secretase) inhibition; phosphoproteomics and p53 tetramer assays; co-IP for GP73-AFP and secretion assays

    PMID:33649292 PMID:33850109 PMID:34650031

    Open questions at the time
    • Mechanism by which GOLM1 restrains Notch undefined
    • Direct vs indirect control of p53 Ser315 phosphorylation unresolved
  16. 2022 High

    Unified the recycling-vs-degradation switch and identified a Golgi/lipid-homeostasis function: GOLM1 binds LC3 via an LIR motif for selective RTK autophagy under cholesterol-mTORC1 control, and is required for sphingolipid balance and Golgi integrity.

    Evidence Co-IP, LIR mutagenesis, autophagic flux, cholesterol/mTORC1 manipulation, in vivo statin+RTK inhibitor therapy; lipidomics, EM, Seahorse on GOLM1-depleted Huh-7 cells

    PMID:35443161 PMID:35948172

    Open questions at the time
    • How lipid homeostasis defects relate to RTK adaptor function unclear
    • In vivo relevance of sphingolipid changes untested
  17. 2022 High

    Identified the secreted ectodomain as a fasting-induced glucogenic hormone acting through hepatic cAMP/PKA, with pathological elevation in SARS-CoV-2 infection.

    Evidence Recombinant GP73 hepatocyte assays, cAMP/PKA inhibitors, neutralizing antibody in mouse-adapted SARS-CoV-2 and fasting models

    PMID:34992299

    Open questions at the time
    • Receptor for circulating GP73 on hepatocytes not identified
    • Relationship to RabGAP-driven hepatic phenotype unclear
  18. 2024 High

    Defined turnover and downstream stress signaling of circulating GP73: ASGR1 binding routes GP73 to lysosomal degradation, while elevated GP73 binds BIP/GRP78 to trigger ER stress and liver injury, and binds STAT3 to drive tumor angiogenesis.

    Evidence Reciprocal co-IP (ASGR1-GP73, GP73-BIP, GP73-STAT3), ASGR1 KO/OE mice with neutralizing antibody rescue in liver injury models; ChIP for c-Myc/histone lactylation and angiogenesis assays

    PMID:38459023 PMID:38939041

    Open questions at the time
    • Whether ER-stress and STAT3 effects are mediated by secreted vs intracellular GP73 not fully resolved
    • Histone-lactylation regulation single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GOLM1's distinct activities — TGN cargo adaptor, LIR-dependent autophagy receptor, TBC Rab-GAP, and secreted glucogenic hormone — are coordinated within one protein, and which Rab substrate and which hepatocyte receptor underlie its enzymatic and hormonal functions.
  • No structural model integrating TBC domain, coiled-coil, and LIR motif
  • Rab-GAP substrate unidentified
  • Receptor mediating circulating GP73 hormone action unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0005198 structural molecule activity 1 GO:0048018 receptor ligand activity 1
Localization
GO:0005794 Golgi apparatus 3 GO:0005576 extracellular region 2 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 1
Partners
APOEASGR1EGFRHSPA5MAP1LC3MAVSSTAT3TRAF6

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 GP73/GOLM1 is an integral membrane protein localized to the Golgi apparatus, as determined by in vitro transcription-translation studies and immunolocalization experiments using epitope-tagged GP73; it is preferentially expressed by epithelial cells and is normally absent from hepatocytes but upregulated in response to viral infection. In vitro transcription-translation, epitope-tag immunolocalization, Northern blot, immunohistochemistry Gene High 10831838
2002 GP73 expression is upregulated at the RNA and protein level by adenovirus infection, and this induction requires the CtBP interaction domain (CID) of the adenoviral E1A protein, as demonstrated by infection with a panel of E1A mutant adenoviruses and transient transfection of wild-type vs. mutant E1A constructs. RNase protection assay, immunoblotting, immunofluorescence, infection with mutant adenoviruses, transient transfection of E1A mutants Virology High 12359426
2007 Soluble GP73 is released from cells by proprotein convertase (furin)-mediated cleavage of its ectodomain. GP73 traffics from the cis-Golgi to the trans-Golgi network and endosomes, and cleavage occurs at a PC consensus site in the endosomal compartment. Alanine substitutions in the PC consensus site blocked both in vitro and in vivo cleavage, establishing the mechanism of GP73 secretion into serum. In vitro cleavage assay with purified furin, site-directed alanine mutagenesis, cleavage-specific antibody, subcellular fractionation/immunofluorescence of endosomes Traffic High 17662025
2008 At least two of three potential N-linked glycosylation sites on GP73 are occupied; the major glycoforms on secreted GP73 are bi-antennary with core fucose, with a smaller fraction of tri- and tetra-antennary structures, and approximately three-quarters of secreted GP73 is fucosylated, as determined by lectin affinity chromatography and mass spectrometry. Lectin affinity chromatography, mass spectrometry, recombinant GP73 expression Journal of cellular biochemistry High 18004786
2008 C-terminal truncation of GP73 in mice (gene-trap approach generating GP73^tr/tr) causes reduced survival, focal segmental glomerulosclerosis, hyaline thrombi in kidneys, and microvesicular hepatic steatosis with nuclear membrane irregularities, indicating that the GP73 C-terminus is essential for normal epithelial cell function in kidney and liver. Gene trap mouse model, histopathology, immunohistochemistry International journal of clinical and experimental pathology Medium 18830387
2010 The Golgi localization of GOLPH2/GOLM1 is determined by its transmembrane domain combined with a positively charged residue in the cytoplasmic N-terminal tail; the C-terminal luminal domain is dispensable for Golgi targeting. Additionally, both endogenous and secreted GOLPH2 exist as disulfide-bonded dimers, and the coiled-coil domain is sufficient for dimerization. Truncation mutant panel, immunofluorescence microscopy, non-reducing SDS-PAGE, domain deletion analysis PloS one High 22140547
2010 GOLPH2/GOLM1 interacts with secretory clusterin (sCLU); the coiled-coil domain of GOLPH2 is sufficient for binding to sCLU, confirmed by yeast two-hybrid screening, intracellular co-immunoprecipitation, and co-localization in the Golgi. Yeast two-hybrid, co-immunoprecipitation, co-localization by immunofluorescence Molecular biology reports Medium 20842452
2012 IL-6 and oncostatin M (OSM) upregulate GP73 mRNA and protein in hepatoma (HepG2) cells via the shared receptor subunit gp130 and correlate with increased STAT3 phosphorylation; maximal induction requires new protein synthesis, suggesting indirect transcriptional regulators are involved. Cytokine treatment of HepG2 cells, Western blot, STAT3 phosphorylation analysis, protein synthesis inhibition with cycloheximide Cancer biomarkers Medium 23144154
2012 The GOLPH2/GOLM1 promoter (2599 bp fragment) is TATA-less and maintains epithelial specificity. A repressive region (−864 to −734 bp), a positive regulatory region (−734 to −421 bp), and a core promoter region (−421 to −79 bp) were identified by deletion analysis. Adenoviral E1A activates GOLPH2 via its CtBP interaction domain; a GC-box motif (−89 to −83 bp) in the core promoter partly mediates E1A transactivation. Promoter cloning, deletion analysis, luciferase reporter assay, E1A transient transfection Biochemical and biophysical research communications Medium 22542941
2014 Epithelium-specific ETS transcription factor ESE-1 directly binds the GP73 promoter and activates GP73 transcription. Both ESE-1 and GP73 are co-induced by IL-1β in hepatocellular carcinoma cells and during liver inflammation in vivo; knockdown of ESE-1 reduces GP73 expression. Promoter reporter assay, ChIP (direct binding to GP73 promoter), siRNA knockdown, overexpression, in vivo liver inflammation model Cell & bioscience Medium 25530841
2014 GP73 enhances HCV secretion through its coiled-coil domain and by interacting with apolipoprotein E (ApoE), a host factor required for HCV secretion; GP73 overexpression or knockdown had no effect on HCV entry, protein translation, RNA replication, or assembly, placing GP73 specifically in the secretion step. Co-immunoprecipitation (GP73-ApoE interaction), GP73 overexpression/knockdown in HCV replicon and infected cell systems, domain deletion (coiled-coil mutant) PloS one Medium 24608522
2015 mTORC1 positively regulates GP73 expression in HCC and other cancer cell lines; rapamycin (mTORC1 inhibitor) reduces GP73 levels in cancer cell lines and in xenograft tumors. GP73 overexpression promotes HCC cell proliferation and migration in vitro and accelerates xenograft tumor growth and metastasis in mice; GP73 knockout mice show reduced liver damage after diethylnitrosamine administration. Retroviral GP73 overexpression, shRNA knockdown, GP73 knockout mice, xenograft mouse models, rapamycin treatment, microarray gene expression, PTEN-null MEFs with constitutively active mTOR Gastroenterology High 25980751
2016 GOLM1 selectively interacts with EGFR and other RTKs and functions as a cargo adaptor to anchor EGFR/RTKs on the trans-Golgi network (TGN) and recycle them back to the plasma membrane, leading to prolonged downstream kinase activation and promoting HCC metastasis. Co-immunoprecipitation (GOLM1-EGFR interaction), gain- and loss-of-function studies, RTK recycling assays, gene expression profiling of HCC tissues Cancer cell High 27569582
2016 N-glycosylation of GP73 at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness; removal of N-glycans at Asn144 by site-directed mutagenesis enhances cell migration and invasion, possibly by altering cell membrane glycosylation and cell adhesion. Three N-glycosylation sites were identified (Asn109, Asn144, Asn398) by mass spectrometry, with five glycoforms at Asn144. Mass spectrometry for glycosylation site mapping, lectin microarray, site-directed mutagenesis of Asn144, cell migration and invasion assays Oncotarget High 26993603
2017 GP73 acts as a negative regulator of innate immunity to facilitate HCV infection: upon HCV infection, MAVS recruits TRAF6 via TRAF-interacting motifs; TRAF6 then directly recruits GP73 to MAVS via GP73's coiled-coil domain. GP73 then promotes proteasome-dependent degradation of both MAVS and TRAF6, attenuating IFN-β and NF-κB signaling. Co-immunoprecipitation (GP73-MAVS, GP73-TRAF6), domain mapping (coiled-coil deletion), proteasome inhibitor experiments, IFN-β/NF-κB reporter assays, GP73 knockdown in primary human hepatocytes and Huh7 cells, rescue with shRNA-resistant GP73 mutant PLoS pathogens High 28394926
2017 GOLM1 promotes prostate cancer progression by activating the PI3K-AKT-mTOR signaling pathway; PI3K inhibitor BKM120 abrogates GOLM1's oncogenic effects on proliferation, migration, invasion, and apoptosis in PCa cell lines and xenograft models. GOLM1 overexpression and knockdown in PCa cell lines, xenograft mouse models, PI3K inhibitor treatment, Western blot for AKT/mTOR pathway components The Prostate Medium 29181846
2017 PDGFA/PDGFRα signaling regulates GOLM1 expression; GOLM1 in turn promotes glioma progression through activation of AKT. GOLM1 is a key element in the PDGFA/PDGFRα-mediated AKT activation cascade, as demonstrated by PDGFRα inhibitor AG1296 and AKT inhibitor MK-2206 experiments. siRNA knockdown and lentiviral overexpression of GOLM1 in glioma cells, PDGFRα inhibitor (AG1296), AKT inhibitor (MK-2206), membrane-based kinase antibody array, orthotopic implantation in vivo Journal of experimental & clinical cancer research Medium 29282077
2019 c-Myc transcriptionally activates GP73 in a mildly hypoxic microenvironment; GP73 then interacts with intracellular MMP-7 via its cytoplasmic domain and facilitates MMP-7 trafficking and secretion, promoting HCC cell metastasis. ChIP assay (c-Myc binding to GP73 promoter), co-immunoprecipitation (GP73-MMP-7), cytoplasmic domain interaction mapping, MMP-7 secretion assays, cell invasion assays Oncogenesis Medium 31591387
2019 mTOR negatively regulates miR-145 expression; miR-145 directly inhibits GOLM1 by targeting its coding sequence. GOLM1-enriched exosomes activate the GSK-3β/MMP signaling axis in recipient cells, accelerating proliferation and migration. miR-145 target validation (luciferase reporter assay targeting CDS of GOLM1), exosome isolation and transfer assay, GSK-3β/MMP pathway analysis, in vivo mouse HCC model Journal of genetics and genomics Medium 31186161
2019 GP73 is a direct transcriptional target of TGF-β1; upregulated GP73 inhibits TGF-β-Smad-mediated growth suppression while enhancing ERK/AKT signaling downstream of TGF-β1. Mechanistically, GP73 upregulates lipid rafts/caveolin-1, which mediates the switch from Smad to non-Smad TGF-β1 signaling. TGF-β1 reporter assay, GP73 overexpression/knockdown, Western blot for Smad and ERK/AKT phosphorylation, lipid raft isolation, caveolin-1 staining Biochimica et biophysica acta. Molecular cell research Medium 30615900
2020 GOLM1 upregulates PD-L1 expression via the EGFR/STAT3 signaling pathway in HCC cells: GOLM1 enhances EGFR levels, which promotes STAT3 phosphorylation, which in turn increases PD-L1 transcription. GOLM1 overexpression/knockdown, Western blot for EGFR and p-STAT3, STAT3 inhibitor treatment, PD-L1 expression analysis American journal of cancer research Medium 33294262
2021 GOLM1 promotes COP9 signalosome 5-mediated PD-L1 deubiquitination in HCC cells, stabilizing PD-L1, and suppresses Rab27b expression to increase transport of PD-L1 into exosomes. Exosomes containing PD-L1 from GOLM1-high HCC cells upregulate PD-L1 on macrophages, inducing CD8+ T cell suppression. Gain- and loss-of-function studies, co-culture assays with exosomes, Rab27b expression analysis, ubiquitination/deubiquitination assays, flow cytometry for CD8+ T cells Signal transduction and targeted therapy Medium 34795203
2021 GOLM1 depletion in intestinal epithelial cells leads to aberrant Notch pathway activation, interfering with IEC differentiation, maturation, and lineage commitment. GOLM1-deficient mice are susceptible to mucosal inflammation and colitis-induced epithelial damage; pharmacological inhibition of Notch alleviates epithelial lesions in GOLM1-deficient mice, placing GOLM1 upstream of Notch equilibrium. GOLM1 knockout mice (colitis models), Notch pathway inhibition (gamma-secretase inhibitor), histopathology, marker gene expression analysis Signal transduction and targeted therapy Medium 33850109
2021 GP73 is a Rab GTPase-activating protein (RabGAP) with TBC domain activity that regulates ApoB export from hepatocytes; liver-specific GP73-overexpressing mice develop non-obese NAFLD (intrahepatic lipid accumulation, insulin resistance, reduced body weight), a phenotype not recapitulated by a GAP-inactive GP73 mutant. Metformin inactivates the GAP activity of GP73 and alleviates this non-obese NAFLD phenotype. RabGAP activity assay, TBC-domain mutagenesis (GAP-inactive mutant), liver-specific GP73 transgenic mice, high-fat diet NAFLD comparison, metformin treatment, ApoB export assays Nature communications High 34853313
2021 GOLM1 promotes liver fibrosis-induced PD-L1 upregulation and immune escape in HCC via the EGFR signaling pathway; GOLM1 levels are increased in fibrotic livers and hepatocyte-specific GOLM1 transgenic mice show decreased CD8+ T cell infiltration and increased PD-L1 in tumors during chemical carcinogenesis. EGFR inhibitors improve immunotherapy efficacy. Hepatocyte-specific GOLM1 transgenic mice, CCl4-induced fibrosis model, EGFR inhibitor treatment, immunohistochemistry for CD8+ T cells and PD-L1, EGFR pathway Western blot Cancer letters Medium 33992711
2021 GP73 directly binds AFP and increases AFP secretion from HCC cells; extracellular GP73 independently promotes HCC cell proliferation and metastasis, and extracellular GP73 and AFP synergize to enhance HCC malignancy and drug resistance to sorafenib. Co-immunoprecipitation (GP73-AFP direct binding), GP73 overexpression/knockdown, AFP secretion assays, cell proliferation and metastasis assays, sorafenib resistance assay Oncogenesis Medium 34650031
2021 GOLM1 overexpression enhances phosphorylation of p53 at Ser315 and inhibits p53 tetramer formation, reducing p53 tumor-suppressor function; this effect is associated with GOLM1-driven lung cancer aggressiveness as shown by phosphoproteomic analysis. Phosphoproteomics (phosphoprotein array), Western blot for p53 phospho-Ser315, p53 tetramer native gel assay, GOLM1 overexpression/knockdown, xenograft in vivo Cell death discovery Medium 33649292
2022 Cholesterol suppresses GOLM1-dependent autophagic degradation of RTKs: GOLM1 mediates selective autophagy of RTKs by interacting with LC3 through an LC3-interacting region (LIR) motif, and this interaction is regulated by a cholesterol-mTORC1 axis. High cholesterol activates mTORC1 to suppress the LIR-LC3 interaction, switching GOLM1 from promoting RTK degradation to promoting RTK recycling. Co-immunoprecipitation (GOLM1-LC3), LIR motif mutagenesis, autophagic flux assays, cholesterol manipulation, mTORC1 inhibition, statin treatment in vivo with RTK inhibitors Cell reports High 35443161
2022 GP73 functions as a glucogenic hormone: fasting induces GP73 secretion from multiple tissues; secreted GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. SARS-CoV-2 infection increases GP73 secretion, and GP73 antibody blockade inhibits excessive gluconeogenesis in SARS-CoV-2-infected mice and lowers fasting blood glucose. GP73 recombinant protein treatment of hepatocytes, cAMP/PKA pathway inhibitors, GP73-neutralizing antibody in mice, mouse-adapted SARS-CoV-2 infection model, fasting experiments in multiple tissues Nature metabolism High 34992299
2024 ASGR1 (asialoglycoprotein receptor 1) directly binds GP73 and facilitates its lysosomal degradation; ASGR1 deficiency increases circulating GP73 levels. Elevated GP73 then interacts with BIP/GRP78 to activate endoplasmic reticulum stress, causing liver injury. GP73 neutralization attenuates ASGR1-deficiency-induced liver injuries. Co-immunoprecipitation (ASGR1-GP73, GP73-BIP), lysosomal degradation assays, ASGR1 knockout and overexpression in mice, GP73-neutralizing antibody rescue experiments, acetaminophen and CCl4 liver injury models Nature communications High 38459023
2024 GP73 promotes HCC tumor angiogenesis by directly binding STAT3 and simultaneously enhancing GRP78-induced endoplasmic reticulum stress; GP73 is activated transcriptionally by histone lactylation and c-Myc, and GP73-mediated STAT3 phosphorylation potentiates pro-angiogenic functions. Co-immunoprecipitation (GP73-STAT3), ChIP for c-Myc and histone lactylation at GP73 locus, in vitro and in vivo angiogenesis assays, single-cell and spatial transcriptomics Research (Washington, D.C.) Medium 38939041
2012 In Xenopus, morpholino-mediated knockdown of golph2/GOLM1 causes edema, enhanced Nephrin expression in the glomus, reduced expression of pronephric tubule/duct markers (atp1b1, ClC-K, NKCC2, NBC1), and expanded WT1 expression, demonstrating that GOLPH2 is required for normal pronephros development by modulating WT1-dependent differentiation of the pronephric field. Morpholino knockdown in Xenopus embryos, in situ hybridization for pronephric marker genes, immunostaining for WT1 PloS one Medium 22719994
2022 GOLM1 depletion in Huh-7 HCC cells causes aberrant accumulation of ceramides, hexosylceramides, dihexosylceramides, sphinganine, sphingosine, ceramide phosphate, and cholesteryl esters, with reduction in phosphatidylethanolamines, demonstrating that GOLM1 is required for normal cellular sphingolipid homeostasis. GOLM1 depletion also disrupts Golgi structure and reduces mitochondrial oxygen consumption, and impairs cell proliferation. siRNA-mediated GOLM1 knockdown, mass spectrometric lipidomics, Seahorse extracellular flux analysis, electron microscopy, immunofluorescence for Golgi structure, cell cycle analysis Journal of lipid research Medium 35948172
2018 GP73 promotes epithelial-mesenchymal transition (EMT) and invasion in HCC partly by activating the TGF-β1/Smad2 signaling pathway; GP73 enhances p-Smad2 and p-Smad3 levels by mediating TGF-β1. Blocking the TGF-β1/Smad pathway with SB431542 partially reverses GP73-driven EMT, but GP73 retains some pro-EMT activity through additional pathways. GP73 overexpression/knockdown in HCC cell lines, Western blot for p-Smad2/3, TGF-β1/Smad pathway inhibitor (SB431542), in vitro invasion assay, in vivo metastasis model Carcinogenesis Medium 29365054

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. Journal of hepatology 299 16137783
2000 GP73, a novel Golgi-localized protein upregulated by viral infection. Gene 219 10831838
2010 Golgi protein 73 (GOLPH2) is a valuable serum marker for hepatocellular carcinoma. Gut 204 20876776
2002 Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease. Hepatology (Baltimore, Md.) 187 12029628
2016 GOLM1 Modulates EGFR/RTK Cell-Surface Recycling to Drive Hepatocellular Carcinoma Metastasis. Cancer cell 186 27569582
2021 GOLM1 exacerbates CD8+ T cell suppression in hepatocellular carcinoma by promoting exosomal PD-L1 transport into tumor-associated macrophages. Signal transduction and targeted therapy 163 34795203
2010 AFP, AFP-L3, DCP, and GP73 as markers for monitoring treatment response and recurrence and as surrogate markers of clinicopathological variables of HCC. Journal of gastroenterology 156 20625772
2004 Disease- and cell-specific expression of GP73 in human liver disease. The American journal of gastroenterology 110 15180730
2009 Golgi phosphoprotein 2 (GOLPH2) expression in liver tumors and its value as a serum marker in hepatocellular carcinomas. Hepatology (Baltimore, Md.) 108 19291786
2013 The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer. Journal of human genetics 106 24284362
2007 Endosomal trafficking and proprotein convertase cleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma. Traffic (Copenhagen, Denmark) 104 17662025
2008 Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer. Neoplasia (New York, N.Y.) 94 18953438
2019 Evaluation of Salivary Exosomal Chimeric GOLM1-NAA35 RNA as a Potential Biomarker in Esophageal Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 82 30745298
2015 mTORC1 Up-Regulates GP73 to Promote Proliferation and Migration of Hepatocellular Carcinoma Cells and Growth of Xenograft Tumors in Mice. Gastroenterology 76 25980751
2019 Ratiometric Immunosensor for GP73 Detection Based on the Ratios of Electrochemiluminescence and Electrochemical Signal Using DNA Tetrahedral Nanostructure as the Carrier of Stable Reference Signal. Analytical chemistry 72 30742421
2008 N-linked glycosylation of the liver cancer biomarker GP73. Journal of cellular biochemistry 72 18004786
2008 GOLPH2 and MYO6: putative prostate cancer markers localized to the Golgi apparatus. The Prostate 66 18543251
2009 GP73, a resident Golgi glycoprotein, is sensibility and specificity for hepatocellular carcinoma of diagnosis in a hepatitis B-endemic Asian population. Medical oncology (Northwood, London, England) 62 19399652
2017 GOLM1 promotes prostate cancer progression through activating PI3K-AKT-mTOR signaling. The Prostate 60 29181846
2019 mTOR/miR-145-regulated exosomal GOLM1 promotes hepatocellular carcinoma through augmented GSK-3β/MMPs. Journal of genetics and genomics = Yi chuan xue bao 55 31186161
2011 Golgi protein 73(GP73), a useful serum marker in liver diseases. Clinical chemistry and laboratory medicine 54 21663469
2024 Integrating Single-Cell and Spatial Transcriptomics to Uncover and Elucidate GP73-Mediated Pro-Angiogenic Regulatory Networks in Hepatocellular Carcinoma. Research (Washington, D.C.) 52 38939041
2011 The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences. PloS one 52 22140547
2022 GP73 is a glucogenic hormone contributing to SARS-CoV-2-induced hyperglycemia. Nature metabolism 51 34992299
2012 Interleukin-6 and oncostatin M are elevated in liver disease in conjunction with candidate hepatocellular carcinoma biomarker GP73. Cancer biomarkers : section A of Disease markers 50 23144154
2010 Up-regulated Golgi phosphoprotein 2 (GOLPH2) expression in lung adenocarcinoma tissue. Clinical biochemistry 49 20501332
2008 Decreased survival and hepato-renal pathology in mice with C-terminally truncated GP73 (GOLPH2). International journal of clinical and experimental pathology 47 18830387
2018 The Clinical Significance of GP73 in Immunologically Mediated Chronic Liver Diseases: Experimental Data and Literature Review. Clinical reviews in allergy & immunology 46 29256057
2021 Liver fibrosis promotes immune escape in hepatocellular carcinoma via GOLM1-mediated PD-L1 upregulation. Cancer letters 45 33992711
2017 GP73 represses host innate immune response to promote virus replication by facilitating MAVS and TRAF6 degradation. PLoS pathogens 45 28394926
2012 GP73 expression and its significance in the diagnosis of hepatocellular carcinoma: a review. International journal of clinical and experimental pathology 44 23119104
2024 Deficiency of ASGR1 promotes liver injury by increasing GP73-mediated hepatic endoplasmic reticulum stress. Nature communications 43 38459023
2021 GOLM1 restricts colitis and colon tumorigenesis by ensuring Notch signaling equilibrium in intestinal homeostasis. Signal transduction and targeted therapy 42 33850109
2013 Serum GP73, a marker for evaluating progression in patients with chronic HBV infections. PloS one 40 23418424
2013 Diagnostic value of immunohistochemical staining of GP73, GPC3, DCP, CD34, CD31, and reticulin staining in hepatocellular carcinoma. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 37 23686365
2017 PDGFA/PDGFRα-regulated GOLM1 promotes human glioma progression through activation of AKT. Journal of experimental & clinical cancer research : CR 36 29282077
2009 Hepatocyte GP73 expression in Wilson disease. Journal of hepatology 36 19596473
2017 miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 28419971
2014 Serum gp73 is also a biomarker for diagnosing cirrhosis in population with chronic HBV infection. Clinical biochemistry 35 25168922
2010 Golgi phosphoprotein 2 (GOLPH2/GP73/GOLM1) interacts with secretory clusterin. Molecular biology reports 34 20842452
2015 A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma. Oncotarget 33 25980438
2021 GP73 is a TBC-domain Rab GTPase-activating protein contributing to the pathogenesis of non-alcoholic fatty liver disease without obesity. Nature communications 31 34853313
2020 LncRNA MALAT1 knockdown inhibits cell migration and invasion by suppressing autophagy through miR-384/GOLM1 axis in glioma. European review for medical and pharmacological sciences 31 32196610
2018 GP73 promotes epithelial-mesenchymal transition and invasion partly by activating TGF-β1/Smad2 signaling in hepatocellular carcinoma. Carcinogenesis 31 29365054
2013 Serum GP73 is complementary to AFP and GGT-II for the diagnosis of hepatocellular carcinoma. Oncology letters 31 24137480
2008 GOLPH2 expression in renal cell cancer. BMC urology 31 19014428
2002 Upregulation of the Golgi protein GP73 by adenovirus infection requires the E1A CtBP interaction domain. Virology 31 12359426
2013 Aberrant chimeric RNA GOLM1-MAK10 encoding a secreted fusion protein as a molecular signature for human esophageal squamous cell carcinoma. Oncotarget 30 24243830
2011 A study of diagnostic value of golgi protein GP73 and its genetic assay in primary hepatic carcinoma. Technology in cancer research & treatment 30 21517136
2019 Golgi Membrane Protein 1 (GOLM1) Promotes Growth and Metastasis of Breast Cancer Cells via Regulating Matrix Metalloproteinase-13 (MMP13). Medical science monitor : international medical journal of experimental and clinical research 29 30695018
2018 A Nonsynonymous Variant in the GOLM1 Gene in Cutaneous Malignant Melanoma. Journal of the National Cancer Institute 29 29659923
2022 Cholesterol suppresses GOLM1-dependent selective autophagy of RTKs in hepatocellular carcinoma. Cell reports 28 35443161
2019 c-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment. Oncogenesis 28 31591387
2018 GP73 promotes invasion and metastasis of bladder cancer by regulating the epithelial-mesenchymal transition through the TGF-β1/Smad2 signalling pathway. Journal of cellular and molecular medicine 28 29349903
2018 DNMT1/miR-200a/GOLM1 signaling pathway regulates lung adenocarcinoma cells proliferation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 29710483
2017 The Value of GPC3 and GP73 in Clinical Diagnosis of Hepatocellular Carcinoma. Clinical laboratory 27 29226636
2017 GOLPH2-regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem-like cells in vitro and in vivo. Acta pharmacologica Sinica 26 28880012
2019 Serum GP73 combined AST and GGT reflects moderate to severe liver inflammation in chronic hepatitis B. Clinica chimica acta; international journal of clinical chemistry 24 30796901
2020 GOLM1 upregulates expression of PD-L1 through EGFR/STAT3 pathway in hepatocellular carcinoma. American journal of cancer research 23 33294262
2014 GP73 is upregulated by hepatitis C virus (HCV) infection and enhances HCV secretion. PloS one 23 24608522
2010 GOLPH2 expression may serve as diagnostic marker in seminomas. BMC urology 23 20184749
2004 GP73 and liver disease: a (Golgi) complex enigma. The American journal of gastroenterology 23 15180731
2016 GP73 N-glycosylation at Asn144 reduces hepatocellular carcinoma cell motility and invasiveness. Oncotarget 22 26993603
2014 GP73, a new marker for diagnosing HBV-ACLF in population with chronic HBV infections. Diagnostic microbiology and infectious disease 22 24560809
2020 Circular RNA 103862 Promotes Proliferation and Invasion of Laryngeal Squamous Cell Carcinoma Cells Through the miR-493-5p/GOLM1 Axis. Frontiers in oncology 21 32850310
2018 MicroRNA-143 regulates cell migration and invasion by targeting GOLM1 in cervical cancer. Oncology letters 21 30405775
2021 The functional landscape of Golgi membrane protein 1 (GOLM1) phosphoproteome reveal GOLM1 regulating P53 that promotes malignancy. Cell death discovery 20 33649292
2017 Silencing of GP73 inhibits invasion and metastasis via suppression of epithelial-mesenchymal transition in hepatocellular carcinoma. Oncology reports 20 28075476
2021 GP73-mediated secretion of AFP and GP73 promotes proliferation and metastasis of hepatocellular carcinoma cells. Oncogenesis 19 34650031
2018 GP73 level determines chemotherapeutic resistance in human hepatocellular carcinoma cells. Journal of Cancer 19 29344288
2021 LINC01977 Promotes Breast Cancer Progression and Chemoresistance to Doxorubicin by Targeting miR-212-3p/GOLM1 Axis. Frontiers in oncology 18 33869063
2020 GP73 facilitates hepatitis B virus replication by repressing the NF-κB signaling pathway. Journal of medical virology 18 32077512
2018 Down-expression of GOLM1 enhances the chemo-sensitivity of cervical cancer to methotrexate through modulation of the MMP13/EMT axis. American journal of cancer research 18 30034935
2021 STAT3 activates the transcription of lncRNA NR2F1-AS1 to promote the progression of melanoma via regulating the miR-493-5p/GOLM1 axis. The journal of gene medicine 17 33822440
2015 Multiple lectin assays for detecting glyco-alteration of serum GP73 in liver diseases. Glycoconjugate journal 17 26342810
2021 Long non-coding RNA TP73-AS1 promotes pancreatic cancer growth and metastasis through miRNA-128-3p/GOLM1 axis. World journal of gastroenterology 16 34007135
2015 Golgi phosphoprotein 2 (GOLPH2) is a novel bile acid-responsive modulator of oesophageal cell migration and invasion. British journal of cancer 16 26461057
2014 Epithelium-Specific ETS (ESE)-1 upregulated GP73 expression in hepatocellular carcinoma cells. Cell & bioscience 16 25530841
2012 Cloning and characterization of human Golgi phosphoprotein 2 gene (GOLPH2/GP73/GOLM1) promoter. Biochemical and biophysical research communications 16 22542941
2010 Analysis of GP73 in patients with HCC as a function of anti-cancer treatment. Cancer biomarkers : section A of Disease markers 16 21694465
2021 Suppression of GOLM1 by EGCG through HGF/HGFR/AKT/GSK-3β/β-catenin/c-Myc signaling pathway inhibits cell migration of MDA-MB-231. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 15 34536514
2021 GOLM1 Drives Colorectal Cancer Metastasis by Regulating Myeloid-derived Suppressor Cells. Journal of Cancer 15 34729117
2019 GOLM1 silencing inhibits the proliferation and motility of human glioblastoma cells via the Wnt/β-catenin signaling pathway. Brain research 15 30935831
2021 Use of GP73 in the diagnosis of non-alcoholic steatohepatitis and the staging of hepatic fibrosis. The Journal of international medical research 14 34772312
2015 Sublingual vein parameters, AFP, AFP-L3, and GP73 in patients with hepatocellular carcinoma. Genetics and molecular research : GMR 14 26125916
2013 CXCL10 decreases GP73 expression in hepatoma cells at the early stage of hepatitis C virus (HCV) infection. International journal of molecular sciences 14 24351813
2019 GP73, a novel TGF-β target gene, provides selective regulation on Smad and non-Smad signaling pathways. Biochimica et biophysica acta. Molecular cell research 13 30615900
2018 Overexpression of GP73 promotes cell invasion, migration and metastasis by inducing epithelial-mesenchymal transition in pancreatic cancer. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 13 30217697
2018 GOLM1 Stimulation of Glutamine Metabolism Promotes Osteoporosis via Inhibiting Osteogenic Differentiation of BMSCs. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 13 30396165
2017 High expression of GP73 in primary hepatocellular carcinoma and its function in the assessment of transcatheter arterial chemoembolization. Oncology letters 13 28943903
2014 Effect of GP73 silencing on proliferation and apoptosis in hepatocellular cancer. World journal of gastroenterology 13 25170213
2013 GP73 is down-regulated in gastric cancer and associated with tumor differentiation. World journal of surgical oncology 13 23742050
2013 GP73 is a potential marker for evaluating AIDS progression and antiretroviral therapy efficacy. Molecular biology reports 13 24068434
2012 Generation and characterization of an anti-GP73 monoclonal antibody for immunoblotting and sandwich ELISA. Journal of biomedical research 13 23554786
2010 Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease. Neurobiology of aging 13 20570408
2022 GOLM1 depletion modifies cellular sphingolipid metabolism and adversely affects cell growth. Journal of lipid research 12 35948172
2020 Dynamic expression of hepatic GP73 mRNA and protein and circulating GP73 during hepatocytes malignant transformation. Hepatobiliary & pancreatic diseases international : HBPD INT 12 32171652
2018 Research progress on GP73 in malignant tumors. OncoTargets and therapy 12 30425529
2017 Association of GOLPH2 expression with survival in non-small-cell lung cancer: clinical implications and biological validation. Biomarkers in medicine 12 28880107
2012 Xenopus as a model system for the study of GOLPH2/GP73 function: Xenopus GOLPH2 is required for pronephros development. PloS one 12 22719994

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