Affinage

G0S2

G0/G1 switch protein 2 · UniProt P27469

Length
103 aa
Mass
11.3 kDa
Annotated
2026-04-28
71 papers in source corpus 23 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

G0S2 is a multifunctional small protein that integrates lipid metabolism, cell proliferation, and apoptosis through distinct protein–protein interactions and an intrinsic enzymatic activity. Its best-characterized role is as a potent endogenous inhibitor of adipose triglyceride lipase (ATGL), binding ATGL's patatin domain through a conserved minimal region (residues 20–44) to suppress intracellular lipolysis; genetic ablation in mice produces leanness, enhanced lipolysis, improved insulin sensitivity, and protection from diet-induced hypertriglyceridemia and atherogenesis through increased LPL activity (PMID:20676045, PMID:25381555, PMID:35026402, PMID:40100923). G0S2 also possesses intrinsic lysophosphatidic acid acyltransferase (LPAAT) activity that promotes triglyceride synthesis independently of ATGL inhibition, localizes to lipid droplets via an ER-to-LD hairpin mechanism, and is regulated post-translationally by K48-linked polyubiquitination at K25 (PMID:30802154, PMID:36420951, PMID:27248498). Beyond lipid metabolism, G0S2 promotes apoptosis by binding Bcl-2 and disrupting Bcl-2/Bax heterodimers, enforces quiescence by sequestering nucleolin in the cytosol, and suppresses oncogenic transformation by repressing MYC-driven transcription (PMID:19706769, PMID:22693613, PMID:26837760). G0S2 transcription is directly activated by RA/RAR, PPARγ, and PML/RARα–C/EBPε co-recruitment, and is repressed by JAZF1–Purβ interaction (PMID:18636162, PMID:24993166, PMID:27605212, PMID:37244968).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2008 High

    Identifying how G0S2 expression is transcriptionally controlled established it as a direct retinoic acid/RAR target in APL cells, revealing a regulatory axis linking differentiation signals to G0S2 induction.

    Evidence Reporter assays with RARE site mutagenesis, cycloheximide-insensitive induction in NB4 APL cells and APL transgenic mice

    PMID:18636162

    Open questions at the time
    • Whether RA/RAR regulation of G0S2 operates in non-hematopoietic tissues
    • Chromatin-level regulation at the G0S2 locus beyond RARE elements
  2. 2009 High

    Determining whether G0S2 has a pro-apoptotic function revealed that it binds Bcl-2 directly and disrupts protective Bcl-2/Bax heterodimers, establishing a death-promoting role independent of Bcl-2 homology domains.

    Evidence Reciprocal co-immunoprecipitation, mitochondrial fractionation, apoptosis assays in cancer cell lines, NF-κB reporter assays

    PMID:19706769

    Open questions at the time
    • Structural basis of the G0S2–Bcl-2 interaction
    • Whether G0S2-mediated apoptosis operates in non-cancer primary cells in vivo
    • Relationship between lipid metabolic and apoptotic functions
  3. 2010 High

    Establishing whether G0S2 directly regulates lipolysis demonstrated that it is a bona fide inhibitor of ATGL, binding independently of ATGL's coactivator CGI-58 and preventing lipid droplet turnover, thus revealing a fundamental metabolic function.

    Evidence Co-immunoprecipitation, overexpression with lipid droplet morphology and lipolysis assays in cultured cells

    PMID:20676045

    Open questions at the time
    • In vivo physiological relevance not yet tested at this point
    • Mechanism by which G0S2 blocks ATGL catalysis
  4. 2011 High

    Mapping the ATGL domain required for G0S2-mediated inhibition showed that the patatin domain (up to Leu254) is the minimal target, defining the molecular interface of inhibition.

    Evidence In vitro lipase activity assays with systematic truncation mutants and homology modeling

    PMID:22039468

    Open questions at the time
    • Atomic-resolution structure of the G0S2–ATGL complex
    • Contribution of individual G0S2 residues not yet resolved
  5. 2012 High

    Discovering that G0S2 enforces hematopoietic stem cell quiescence by sequestering nucleolin in the cytosol revealed a proliferation-regulatory function mechanistically distinct from its metabolic role.

    Evidence Retroviral overexpression and shRNA knockdown in primary HSCs, proteomic pulldown identifying nucleolin, subcellular fractionation, bone marrow transplantation

    PMID:22693613

    Open questions at the time
    • Whether nucleolin sequestration contributes to quiescence in non-hematopoietic cell types
    • How G0S2's hydrophobic domain interacts with nucleolin's RGG domain at structural level
  6. 2013 High

    In vivo gain-of-function in adipose-specific transgenic mice confirmed G0S2 as a physiological brake on lipolysis, showing it controls whole-body fuel selection during fasting.

    Evidence Transgenic mouse overexpression in adipose, β3-agonist stimulated lipolysis, metabolic phenotyping, electron microscopy of brown adipocyte lipid droplets

    PMID:24302733

    Open questions at the time
    • Contribution of G0S2 in non-adipose tissues to systemic lipid metabolism
    • Whether G0S2 LPAAT activity contributes to the transgenic phenotype
  7. 2014 High

    Loss-of-function in G0s2 knockout mice demonstrated that endogenous G0S2 restrains adiposity, thermogenesis, and glucose homeostasis, firmly positioning it as a therapeutic target in metabolic disease.

    Evidence G0s2 knockout mice with body composition, glucose/insulin tolerance, calorimetry, cold tolerance, independently replicated

    PMID:24556704 PMID:25381555

    Open questions at the time
    • Tissue-specific contributions (adipose vs. liver vs. other) not dissected
    • Mechanism linking enhanced lipolysis to white adipose browning
  8. 2014 Medium

    Identifying PPARγ as a direct transcriptional activator of G0S2 in adipocytes, and showing TNF-α represses G0S2 by degrading PPARγ, connected inflammatory and metabolic regulation of lipolysis at the transcriptional level.

    Evidence ChIP showing PPARγ occupancy at G0S2 promoter, MG-132 rescue, PPARγ overexpression, lipolysis assays

    PMID:24993166

    Open questions at the time
    • Whether other PPAR isoforms regulate G0S2 in liver or muscle
    • Genome-wide context of PPARγ-dependent G0S2 regulation
  9. 2015 High

    Demonstrating that G0S2 suppresses oncogenic transformation independently of ATGL inhibition, by repressing a MYC-regulated transcriptional program, established G0S2 as a tumor suppressor with a lipolysis-independent mechanism.

    Evidence G0s2-null MEFs transformed by HRAS/EGFR, rescued by MYC RNAi/pharmacologic inhibition, genome-wide expression analysis

    PMID:26837760

    Open questions at the time
    • How G0S2 mechanistically represses MYC activity (direct vs. indirect)
    • In vivo tumor suppressor function in spontaneous cancer models
  10. 2015 Medium

    Showing G0S2 inhibits oxidative phosphorylation in naïve CD8+ T cells linked its metabolic function to immune cell bioenergetics and quiescence control.

    Evidence G0s2 knockout mice, Seahorse respirometry, AMPK phosphorylation analysis, in vivo lymphopenia-induced proliferation

    PMID:25666096

    Open questions at the time
    • Whether the effect on OXPHOS is ATGL-dependent or ATGL-independent
    • Functional consequences for antigen-specific T cell responses in vivo
    • Single-lab finding
  11. 2016 High

    Identifying K48-linked polyubiquitination at K25 as the post-translational signal for G0S2 proteasomal degradation, and showing ATGL and triglycerides stabilize G0S2 protein, revealed a feedback loop coupling lipolytic flux to inhibitor abundance.

    Evidence K25R mutagenesis, ubiquitination assays, proteasome inhibitor treatment, ATGL knockout mouse adipose analysis

    PMID:27248498

    Open questions at the time
    • Identity of the E3 ubiquitin ligase targeting G0S2
    • Whether K25 ubiquitination is regulated by upstream signaling
  12. 2016 High

    Showing that PML/RARα and C/EBPε cooperatively activate G0S2 transcription during ATRA-induced APL differentiation defined a ligand-dependent nuclear receptor mechanism for G0S2 induction in myeloid cells.

    Evidence ChIP-qPCR, reciprocal co-immunoprecipitation of PML/RARα–C/EBPε, luciferase reporters, primary APL cells

    PMID:27605212

    Open questions at the time
    • Whether this cooperative mechanism operates at other G0S2 target genes
    • Relevance in non-APL myeloid differentiation
  13. 2019 High

    Discovering that G0S2 possesses intrinsic LPAAT enzymatic activity, promoting triglyceride synthesis independently of ATGL inhibition, fundamentally expanded its functional repertoire from inhibitor to enzyme.

    Evidence In vitro LPAAT assay, mutagenesis of 4-aa LPAAT motif, ATGL-null hepatocytes with G0S2 knockdown, 14C-fatty acid incorporation, high-sucrose diet model

    PMID:30802154

    Open questions at the time
    • Structural basis of LPAAT activity
    • Relative physiological contribution of LPAAT vs. ATGL-inhibitory functions in different tissues
  14. 2020 High

    Demonstrating that zebrafish g0s2 maintains mitochondrial ATP production in cardiomyocytes under hypoxia extended G0S2's function to ischemic tolerance, linking its metabolic roles to cardiac stress protection.

    Evidence TALEN knockout and cardiomyocyte-specific transgenic zebrafish, FRET-based mitochondrial ATP biosensor, cardiac contractility measurement

    PMID:31916304

    Open questions at the time
    • Whether this cardioprotective effect operates in mammalian hearts
    • Molecular mechanism connecting G0S2 to mitochondrial ATP maintenance under hypoxia
  15. 2022 High

    Systematic per-residue mutagenesis of the G0S2 20–44 region defined the key inhibitory residues (Y27, V28, G30, A34, G37, V39, L42) and demonstrated cross-species conservation of the ATGL-inhibitory mechanism from platypus to human.

    Evidence Site-directed mutagenesis, in vitro ATGL activity assays with truncation peptides, cross-species ortholog functional comparison

    PMID:35026402

    Open questions at the time
    • No co-crystal structure of G0S2 peptide with ATGL patatin domain
    • Whether inhibitory potency varies among orthologs in vivo
  16. 2022 Medium

    Determining how G0S2 reaches lipid droplets revealed a hairpin topology with two hydrophobic segments and positively charged hinge residues sorting it from ER to LDs, with an alternative ATGL-dependent targeting pathway.

    Evidence Mutagenesis of hydrophobic sequences and hinge charges, live-cell fluorescence microscopy, ATGL co-expression rescue

    PMID:36420951

    Open questions at the time
    • Whether G0S2 LD targeting is regulated by metabolic signals
    • Topology of G0S2 within the LD phospholipid monolayer at structural resolution
    • Single-lab finding
  17. 2023 Medium

    Identifying JAZF1–Purβ as a repressor of G0S2 transcription in endometrial stromal cells linked G0S2 to decidualization and endometrial function.

    Evidence JAZF1 knockdown, co-immunoprecipitation of JAZF1–Purβ, ChIP of Purβ at G0S2 promoter, apoptosis and decidualization marker assays in hESCs

    PMID:37244968

    Open questions at the time
    • Whether JAZF1–Purβ regulation of G0S2 operates in other tissues
    • In vivo relevance in uterine biology
  18. 2025 High

    Showing that G0S2 ablation abolishes diet-induced hypertriglyceridemia and attenuates atherogenesis by increasing LPL activity from white adipose tissue connected intracellular ATGL-dependent lipolysis to extracellular triglyceride clearance, establishing G0S2 as a regulator of systemic lipid homeostasis.

    Evidence G0S2 knockout mice, WAT transplantation, LPL activity assays, ATGL inhibitor reversal, ANGPTL4 analysis, atherogenesis quantification

    PMID:40100923

    Open questions at the time
    • Mechanism linking intracellular lipolysis to LPL stabilization/secretion
    • Therapeutic potential of G0S2 inhibition in humans

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of the G0S2–ATGL complex, the identity of the E3 ligase mediating K25 ubiquitination, how G0S2 mechanistically represses MYC, and the relative tissue-specific contributions of LPAAT vs. ATGL-inhibitory activities to systemic metabolism.
  • No co-crystal or cryo-EM structure of G0S2 with ATGL
  • E3 ubiquitin ligase for G0S2 unidentified
  • Mechanism of MYC repression not defined
  • Tissue-specific balance of LPAAT vs. anti-lipolytic functions unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0140313 molecular sequestering activity 2 GO:0016740 transferase activity 1
Localization
GO:0005739 mitochondrion 2 GO:0005783 endoplasmic reticulum 2 GO:0005811 lipid droplet 2 GO:0005768 endosome 1
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 2 R-HSA-5357801 Programmed Cell Death 1
Partners
BCL2CEBPENCLPNPLA2PPARGPURB

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 G0S2 encodes a mitochondrial protein that specifically interacts with Bcl-2 and promotes apoptosis by preventing the formation of protective Bcl-2/Bax heterodimers. G0S2 lacks Bcl-2 homology domains but directly binds Bcl-2. Its expression is induced by TNF-α through NF-κB. Co-immunoprecipitation, subcellular fractionation (mitochondrial localization), ectopic expression in cancer cell lines, apoptosis assays, NF-κB reporter assays Cancer research High 19706769
2010 G0S2 acts as a direct inhibitor of adipose triglyceride lipase (ATGL) activity and ATGL-mediated lipolysis. G0S2 binds ATGL independently of ATGL's activity state or the presence of the coactivator CGI-58. CGI-58 and G0S2 regulate ATGL via non-competing mechanisms. G0S2 expression prevents LD turnover even when CGI-58 and ATGL are co-expressed. Co-immunoprecipitation, overexpression in cells, lipid droplet morphology assays, lipolysis assays Cell cycle (Georgetown, Tex.) High 20676045
2011 The minimal active domain of ATGL sufficient for inhibition by G0S2 and activation by CGI-58 ranges from amino acids up to leucine 254, corresponding to an extended patatin domain. G0S2 inhibits this minimal domain and mediates protein-protein interaction with it. In vitro lipase activity assays with truncation mutants, protein-protein interaction assays, 3D homology modeling PloS one High 22039468
2012 G0S2 localizes to the mitochondria, endoplasmic reticulum, and early endosomes in hematopoietic cells. G0S2 promotes quiescence in hematopoietic stem cells (HSCs) by interacting with nucleolin via the hydrophobic domain of G0S2 binding to the arginine-glycine-glycine repeat domain of nucleolin, resulting in cytosolic retention of nucleolin and preventing its pro-proliferative functions in the nucleolus. Retroviral overexpression, co-transplantation bone marrow assays, shRNA knockdown, proteomic pulldown, subcellular fractionation/localization (immunofluorescence), cell cycle analysis PloS one High 22693613
2013 G0S2 inhibits proliferation of K562 leukemia cells by sequestering the nucleolar phosphoprotein nucleolin in the cytosol, preventing its pro-proliferative nucleolar functions. Knockdown of G0S2 restores proliferation in cells where G0S2 was induced by demethylation. shRNA knockdown, overexpression, 5-azacytidine demethylation, cell proliferation assays, xenograft models, nucleolin localization studies Leukemia research Medium 24183236
2013 Adipose-specific overexpression of G0S2 in transgenic mice defects basal and adrenergically stimulated lipolysis, increases fat mass, decreases peripheral triglyceride accumulation, prevents the switch from carbohydrate to fatty acid utilization during fasting, and causes accumulation of larger lipid droplets in brown adipocytes, confirming G0S2 as a physiological inhibitor of ATGL-mediated lipolysis in vivo. Adipose-specific transgenic mouse model, in vivo lipolysis assays (fasting, β3-agonist injection), adipose explant lipolysis, metabolic phenotyping, electron microscopy The Journal of biological chemistry High 24302733
2014 G0s2 knockout mice are lean, resistant to high-fat diet-induced weight gain, glucose tolerant, and insulin sensitive. Adipocytes from G0s2-/- mice show enhanced lipase activity and stimulated lipolysis. Energy metabolism is shifted toward lipid utilization and increased thermogenesis, with enhanced browning of white adipose tissue. This confirms G0S2 as a physiological regulator of ATGL-dependent lipolysis and adiposity in vivo. G0s2 knockout mouse model, body composition analysis, glucose/insulin tolerance tests, in vitro and in vivo lipolysis assays, calorimetry, cold tolerance tests, gene expression analysis Diabetologia High 24556704 25381555
2015 G0S2 suppresses oncogenic transformation independently of ATGL inhibition by repressing a MYC-regulated transcriptional program. G0s2-null MEFs are readily transformed by HRAS or EGFR, and this transformation is abrogated by RNAi or pharmacologic inhibition of MYC. Gene expression analysis revealed upregulation of MYC target gene signatures in G0s2-null MEFs. G0s2-null mouse embryonic fibroblasts (MEFs), oncogenic transformation assays (HRAS, EGFR), RNAi knockdown, pharmacologic MYC inhibition, genome-wide gene expression analysis, rescue experiments Cancer research High 26837760
2015 G0S2 inhibits oxidative phosphorylation in naïve CD8+ T cells. G0S2-null naïve CD8+ T cells display increased basal and spare respiratory capacity associated with increased AMPK-α phosphorylation, without increased mitochondrial biogenesis. G0S2 expression in naïve CD8+ T cells decreases downstream of TCR activation via MAPK, calcium/calmodulin, PI3K and mTOR pathways. G0s2 knockout mice, Seahorse respirometry (oxidative phosphorylation measurement), flow cytometry, mitochondrial biogenesis assays, AMPK phosphorylation western blot, in vitro T cell activation, in vivo lymphopenia-induced proliferation Immunology and cell biology Medium 25666096
2016 G0S2 protein is degraded via the proteasomal pathway initiated by K48-linked polyubiquitination at lysine-25. Mutation of K25 abolishes ubiquitination and increases G0S2 protein stability. G0S2 is stabilized by ATGL expression and by fatty acid-induced triglyceride accumulation through distinct mechanisms. ATGL-deficient mice show reduced G0S2 protein (but not mRNA) in adipose tissue, corroborating ATGL-dependent G0S2 stabilization. Site-directed mutagenesis (K25R), ubiquitination assays, proteasome inhibitor treatment, co-expression studies, ATGL knockout mice, western blotting PloS one High 27248498
2008 G0S2 is a direct transcriptional target of retinoic acid (RA)/RAR signaling in acute promyelocytic leukemia (APL) cells. Retinoic acid response element (RARE) half-sites in the G0S2 promoter mediate RA-induced transcriptional activation. Mutation of RARE sites blocks RA-induced G0S2 activation. G0S2 protein is rapidly induced in NB4 APL cells and in APL transgenic mice treated with RA. RT-PCR, heteronuclear PCR (cycloheximide treatment to show direct target), reporter plasmid with RAR co-transfection, site-directed mutagenesis of RARE sites, protein expression analysis by western blot, pan-RAR antagonist treatment International journal of oncology High 18636162
2016 G0S2 represses PI3K/mTOR signaling in breast cancer cells. Restoring G0S2 expression in ER+ breast cancer cells decreased basal mTOR signaling and sensitized cells to mTOR pathway inhibitors. Genome-wide expression analysis in G0S2-null cells showed enrichment of PI3K/mTOR pathway gene signatures. Genome-wide expression analysis, mTOR signaling western blotting (phospho-Akt, phospho-S6K), pharmacologic mTOR inhibitor sensitivity assays, G0S2 overexpression in breast cancer cell lines Cell cycle (Georgetown, Tex.) Medium 28910567
2019 G0S2 has an intrinsic lysophosphatidic acid acyltransferase (LPAAT) activity that mediates phosphatidic acid synthesis from LPA and acyl-CoA, directly promoting triglyceride synthesis independently of ATGL inhibition. Knockdown of G0S2 decreases hepatic TG content even in ATGL-ablated mice. Deletion of a 4-aa motif necessary for LPAAT activity impairs G0S2's ability to mediate TG synthesis in vitro and in vivo. In vitro LPAAT enzymatic assay, ATGL knockout hepatocytes with G0S2 knockdown/overexpression, site-directed mutagenesis (4-aa LPAAT motif deletion), fatty acid incorporation assays (14C-labeled), in vivo high-sucrose diet model FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 30802154
2019 High G0S2 expression in glioma stem-like cells (GSCs) promotes radioresistance by reducing lipid droplet turnover, which attenuates RNF168-mediated 53BP1 ubiquitination through activation of mTOR-S6K signaling, thereby increasing 53BP1 protein stability, enhancing DNA repair, and promoting radioresistance. RNA-seq in radioresistant GSCs, G0S2 knockdown/overexpression, lipid droplet quantification (immunofluorescence), γ-H2AX foci assay, 53BP1 ubiquitination assay, mTOR-S6K western blotting, xenograft survival studies Journal of experimental & clinical cancer research : CR Medium 30953555
2020 G0s2 in zebrafish provides ischemic/hypoxic tolerance in cardiomyocytes by maintaining mitochondrial ATP production under hypoxia. Zebrafish with TALEN-mediated g0s2 knockout lose hypoxic tolerance, while cardiomyocyte-specific g0s2 transgenic zebrafish exhibit strong hypoxic tolerance. Real-time mitochondrial ATP imaging showed g0s2-expressing cardiomyocytes maintain intra-mitochondrial ATP concentration and contractility under hypoxia. TALEN knockout zebrafish, cardiomyocyte-specific transgenic zebrafish, mitochondrially targeted FRET-based ATP biosensor (in vivo imaging), mosaic overexpression model, cardiac contractility measurement FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 31916304
2022 G0S2 localizes to lipid droplets (LDs) via a hairpin structure consisting of two hydrophobic sequences that mediates ATGL-independent localization to both the endoplasmic reticulum (ER) and LDs. Positively charged residues in the hinge region sort G0S2 from the ER to LDs. When ATGL is co-expressed, these positive charges become dispensable for LD targeting, revealing an ATGL-dependent LD targeting mechanism as well. Structural prediction, site-directed mutagenesis (hydrophobic sequences, hinge positive charges), fluorescence microscopy in cells, ATGL co-expression experiments Journal of cell science Medium 36420951
2022 The minimal sequence of G0S2 required for ATGL inhibition spans amino acids 20–44, with key residues Y27, V28, G30, A34, G37, V39, and L42 playing substantial roles in ATGL inhibition. N-terminal extensions (aa 20–27) contribute unspecific interactions that facilitate ATGL binding. G0S2 orthologs from platypus, chicken, and Japanese rice-fish can inhibit human and mouse ATGL, confirming conservation of the inhibitory mechanism. Site-directed mutagenesis, truncation studies, in vitro ATGL lipase activity assays, cross-species functional comparison Biochimica et biophysica acta. Molecular and cell biology of lipids High 35026402
2016 During ATRA-induced APL differentiation, G0S2 transcription is activated by coordinated recruitment of PML/RARα and the C/EBPε p30 isoform to the G0S2 promoter. PML/RARα physically interacts with C/EBPε and cooperates functionally to upregulate G0S2. This represents a type I nuclear receptor mode of action for PML/RARα (ligand-dependent DNA binding). Chromatin immunoprecipitation (ChIP)-qPCR, co-immunoprecipitation (physical PML/RARα–C/EBPε interaction), luciferase reporter assays, primary APL cell analysis Journal of leukocyte biology High 27605212
2014 TNF-α reduces G0S2 expression in adipocytes through proteasomal degradation of PPARγ, which normally binds the G0S2 promoter. The proteasomal inhibitor MG-132 maintains PPARγ levels and prevents TNF-α-induced loss of PPARγ occupancy at the G0S2 promoter, demonstrating that G0S2 transcription depends on PPARγ binding and that TNF-α represses G0S2 by eliminating its transcriptional activator. Promoter ChIP (PPARγ binding to G0S2 promoter), PPARγ overexpression, MG-132 proteasome inhibition, western blotting, lipolysis assay, G0S2 overexpression rescue Cytokine Medium 24993166
2023 JAZF1 represses G0S2 transcription in human endometrial stromal cells (hESCs) by interacting with the G0S2 transcriptional activator Purβ, restricting Purβ activity. G0S2 upregulation upon JAZF1 depletion drives hESC apoptosis and defective decidualization. JAZF1 knockdown in hESCs, G0S2 knockdown rescue experiments, co-immunoprecipitation (JAZF1-Purβ interaction), chromatin immunoprecipitation (Purβ at G0S2 promoter), apoptosis assays, decidualization markers Communications biology Medium 37244968
2025 Genetic ablation of G0S2 completely abolishes diet-induced hypertriglyceridemia and attenuates atherogenesis in mice by enhancing whole-body triglyceride clearance. G0S2 deletion increases circulating LPL concentration and activity predominantly through LPL production from white adipose tissue (WAT), associated with improved insulin sensitivity and decreased ANGPTL4 expression. Transplantation of G0S2-deficient WAT normalizes plasma TG in hypertriglyceridemic mice, and this LPL-stabilizing effect is reversed by ATGL inhibition, linking intracellular ATGL activity to extracellular LPL stability. G0S2 knockout mice, WAT transplantation, LPL activity/concentration assays, ATGL inhibitor treatment, ANGPTL4 expression analysis, atherogenesis quantification, tissue-specific rescue experiments The Journal of clinical investigation High 40100923
2024 In a mouse model of brain-evoked depletion of all fat depots, catecholamine-independent lipolysis is driven by downregulation of cell-autonomous lipolytic inhibitors including G0s2 (along with Acvr1c and Npr3). This G0s2 downregulation during concurrent hypoglycemia and hypoinsulinemia activates ATGL-dependent lipolysis independently of the sympathetic nervous system. Genetic knockout mice (G0s2 and ATGL), surgical denervation, chemical sympathectomy, metabolic phenotyping, gene expression analysis, lipid droplet imaging bioRxivpreprint Medium bio_10.1101_2024.07.30.605812

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer research 114 19706769
2012 The G0/G1 switch gene 2 (G0S2): regulating metabolism and beyond. Biochimica et biophysica acta 105 23032787
2010 Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2. Cell cycle (Georgetown, Tex.) 95 20676045
2011 The minimal domain of adipose triglyceride lipase (ATGL) ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively. PloS one 77 22039468
2011 Fasting, but not exercise, increases adipose triglyceride lipase (ATGL) protein and reduces G(0)/G(1) switch gene 2 (G0S2) protein and mRNA content in human adipose tissue. The Journal of clinical endocrinology and metabolism 73 21613358
2017 G0S2: A small giant controller of lipolysis and adipose-liver fatty acid flux. Biochimica et biophysica acta. Molecular and cell biology of lipids 72 28645852
2015 Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells. Oncotarget 69 26318046
2019 Targeted Assessment of G0S2 Methylation Identifies a Rapidly Recurrent, Routinely Fatal Molecular Subtype of Adrenocortical Carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 54 30770352
2010 Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches. International journal of cancer 53 19816938
2013 Defective adipose lipolysis and altered global energy metabolism in mice with adipose overexpression of the lipolytic inhibitor G0/G1 switch gene 2 (G0S2). The Journal of biological chemistry 52 24302733
2012 The cytosolic protein G0S2 maintains quiescence in hematopoietic stem cells. PloS one 48 22693613
2014 TNF-α reduces g0s2 expression and stimulates lipolysis through PPAR-γ inhibition in 3T3-L1 adipocytes. Cytokine 44 24993166
1997 Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells. DNA and cell biology 43 9428793
2014 Deletion of the gene encoding G0/G 1 switch protein 2 (G0s2) alleviates high-fat-diet-induced weight gain and insulin resistance, and promotes browning of white adipose tissue in mice. Diabetologia 40 25381555
2016 G0S2 Suppresses Oncogenic Transformation by Repressing a MYC-Regulated Transcriptional Program. Cancer research 38 26837760
2017 Palmitate induces fat accumulation by activating C/EBPβ-mediated G0S2 expression in HepG2 cells. World journal of gastroenterology 37 29209111
2008 G0S2 is an all-trans-retinoic acid target gene. International journal of oncology 37 18636162
2009 Impact of DNA demethylation of the G0S2 gene on the transcription of G0S2 in squamous lung cancer cell lines with or without nuclear receptor agonists. Biochemical and biophysical research communications 36 19878646
2022 Single-Cell Sequencing Analysis and Multiple Machine Learning Methods Identified G0S2 and HPSE as Novel Biomarkers for Abdominal Aortic Aneurysm. Frontiers in immunology 35 35769488
2018 Disruption of G0/G1 switch gene 2 ( G0S2) reduced abdominal fat deposition and altered fatty acid composition in chicken. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 33 30085885
2014 Mice lacking G0S2 are lean and cold-tolerant. Cancer biology & therapy 32 24556704
2019 Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response. Journal of experimental & clinical cancer research : CR 31 30953555
2013 G0S2 inhibits the proliferation of K562 cells by interacting with nucleolin in the cytosol. Leukemia research 31 24183236
1998 An alternative way of thinking about stem-loops in DNA. A case study of the human G0S2 gene. Journal of theoretical biology 27 9680722
2020 Cooperative application of transcriptomics and ceRNA hypothesis: LncRNA-107052630/miR-205a/G0S2 crosstalk is involved in ammonia-induced intestinal apoptotic injury in chicken. Journal of hazardous materials 26 32334290
2013 Porcine G₀/G₁ switch gene 2 (G0S2) expression is regulated during adipogenesis and short-term in-vivo nutritional interventions. Lipids 23 23322075
2023 Acidosis-induced regulation of adipocyte G0S2 promotes crosstalk between adipocytes and breast cancer cells as well as tumor progression. Cancer letters 19 37442366
2016 Regulation of G0/G1 Switch Gene 2 (G0S2) Protein Ubiquitination and Stability by Triglyceride Accumulation and ATGL Interaction. PloS one 18 27248498
2022 G0S2 regulates innate immunity in Kawasaki disease via lncRNA HSD11B1-AS1. Pediatric research 16 35292727
2019 Identification of an intrinsic lysophosphatidic acid acyltransferase activity in the lipolytic inhibitor G0/G1 switch gene 2 (G0S2). FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 30802154
2015 G0S2 modulates homeostatic proliferation of naïve CD8⁺ T cells and inhibits oxidative phosphorylation in mitochondria. Immunology and cell biology 16 25666096
2022 Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism. Clinical and translational medicine 15 36536477
2017 G0S2 represses PI3K/mTOR signaling and increases sensitivity to PI3K/mTOR pathway inhibitors in breast cancer. Cell cycle (Georgetown, Tex.) 15 28910567
2018 The Nuclear Orphan Receptor Nur77 Alleviates Palmitate-induced Fat Accumulation by Down-regulating G0S2 in HepG2 Cells. Scientific reports 14 29556076
2016 Pronounced expression of the lipolytic inhibitor G0/G1 Switch Gene 2 (G0S2) in adipose tissue from brown bears (Ursus arctos) prior to hibernation. Physiological reports 14 27117803
2014 Progesterone-induced down-regulation of hormone sensitive lipase (Lipe) and up-regulation of G0/G1 switch 2 (G0s2) genes expression in inguinal adipose tissue of female rats is reflected by diminished rate of lipolysis. The Journal of steroid biochemistry and molecular biology 14 25448749
2015 Increases in skeletal muscle ATGL and its inhibitor G0S2 following 8 weeks of endurance training in metabolically different rat skeletal muscles. American journal of physiology. Regulatory, integrative and comparative physiology 13 26511521
2022 Residues of the minimal sequence of G0S2 collectively contribute to ATGL inhibition while C-and N-terminal extensions promote binding to ATGL. Biochimica et biophysica acta. Molecular and cell biology of lipids 11 35026402
2020 In vivo real-time ATP imaging in zebrafish hearts reveals G0s2 induces ischemic tolerance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 31916304
2023 JAZF1 safeguards human endometrial stromal cells survival and decidualization by repressing the transcription of G0S2. Communications biology 10 37244968
2021 Promotion effect of salt on intramuscular neutral lipid hydrolysis during dry-salting process of porcine (biceps femoris) muscles by inducing phosphorylation of ATGL, HSL and their regulatory proteins of Perilipin1, ABHD5 and G0S2. Food chemistry 9 34815115
2016 Liver-specific G0 /G1 switch gene 2 (G0s2) expression promotes hepatic insulin resistance by exacerbating hepatic steatosis in male Wistar rats. Journal of diabetes 9 27624922
2023 G0S2 promotes antiestrogenic and pro-migratory responses in ER+ and ER- breast cancer cells. Translational oncology 8 37086619
2022 G0S2 Gene Polymorphism and Its Relationship with Carcass Traits in Chicken. Animals : an open access journal from MDPI 7 35405904
2020 The Expression Pattern and Regulatory Mechanism of the G0/G1 Switch Gene 2 (G0S2) in the Pathogenesis and Treatment of AChR Myasthenia Gravis (MG). Mediators of inflammation 6 33061827
2016 Regulation of G0/G1 switch gene 2 (G0S2) expression in human adipose tissue. Archives of physiology and biochemistry 6 26707160
2025 FXR as a pivotal role linking JNK and G0s2 mitigates triptolide-induced hepatotoxicity through the regulation of metabolic disorder of liver. Pharmacological research 5 40288593
2022 G0S2 ameliorates oxidized low-density lipoprotein-induced vascular endothelial cell injury by regulating mitochondrial apoptosis. Annals of translational medicine 5 36660674
2015 Characterization of lipolytic inhibitor G(0)/G(1) switch gene-2 protein (G0S2) expression in male Sprague-Dawley rat skeletal muscle compared to relative content of adipose triglyceride lipase (ATGL) and comparitive gene identification-58 (CGI-58). PloS one 5 25811590
2014 Tissue expression pattern and polymorphism of G0S2 gene in porcine. Gene 5 24487091
2022 Identification of motifs and mechanisms for lipid droplet targeting of the lipolytic inhibitors G0S2 and HIG2. Journal of cell science 4 36420951
2016 Activation of G0S2 is coordinated by recruitment of PML/RARα and C/EBPε to its promoter during ATRA-induced APL differentiation. Journal of leukocyte biology 4 27605212
2025 Absence of the intracellular lipolytic inhibitor G0S2 enhances intravascular triglyceride clearance and abolishes diet-induced hypertriglyceridemia. The Journal of clinical investigation 2 40100923
2025 Recent advances on the role of G0S2. Discover oncology 2 40679675
2024 Mutation on JmjC domain of UTX impaired its antitumor effects in pancreatic cancer via inhibiting G0S2 expression and activating the Toll-like signaling pathway. Molecular medicine (Cambridge, Mass.) 2 39707168
2023 The effect of G0S2 on insulin sensitivity: A proteomic analysis in a G0S2-overexpressed high-fat diet mouse model. Frontiers in endocrinology 2 37033250
2021 Biophysical characterization and a roadmap towards the NMR solution structure of G0S2, a key enzyme in non-alcoholic fatty liver disease. PloS one 2 34260600
2019 Correction to: Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response. Journal of experimental & clinical cancer research : CR 2 31358019
2015 Deletion of the putative tumor suppressor gene, G0s2, does not affect progression of Eμ-Myc driven lymphomas in mice. Leukemia research 2 26654706
2026 An Extracellular Matrix-Producing Subset of Cancer-Associated Fibroblasts Drives Chemoresistance in Breast Cancer via SRC Activation and G0S2 Upregulation. Cancer research 1 41223328
2025 The Evaluation of PNPLA2, ATGL, and G0S2 Levels in Serum and PBMCs of the Newly Diagnosed and the Chronic Patients With Rheumatoid Arthritis. International journal of rheumatic diseases 1 39989302
2025 The Effect of G0S2 Gene Knockout on the Proliferation, Apoptosis, and Differentiation of Chicken Preadipocytes. Animals : an open access journal from MDPI 1 40218345
2025 BCL2A1‑ and G0S2‑driven neutrophil extracellular traps: A protective mechanism linking preeclampsia to reduced breast cancer risk. Oncology reports 1 40242964
2025 G0S2 Promotes PD-L1 Expression in Monocytes and Influences the Efficacy of PD-1 Inhibitors in Hepatocellular Carcinoma. Genes 1 40282408
2025 PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Epigenetics 1 40568952
2023 Gastric Cancer Growth Modulated by circSNTB2/miR-6938-5p/G0S2 and PDCD4. Combinatorial chemistry & high throughput screening 1 36366842
2026 G0S2 drives lipid metabolism disorders and oxidative stress to promote M1 macrophage polarization and inflammation in polycystic ovary syndrome. Life sciences 0 41985712
2025 G0S2 modulates normal vitreous-induced proliferation in endothelial cells. Communications biology 0 40185884
2025 Metabolic profiling of glioblastoma and identification of G0S2 as a metabolic target. Frontiers in oncology 0 40519301
2024 The repression of the lipolytic inhibitor G0s2 enhancers affects lipid metabolism. Gene 0 39667714
2019 Correction to: Lipolytic inhibitor G0S2 modulates glioma stem-like cell radiation response. Journal of orthopaedic surgery and research 0 31311601