{"gene":"VGLL1","run_date":"2026-06-11T09:02:06","timeline":{"discoveries":[{"year":1999,"finding":"Human TONDU (TDU/VGLL1) contains a short domain homologous to the Drosophila Vestigial (Vg) domain required for interaction with Scalloped (Sd), and specifically interacts with a conserved domain present in all mammalian TEF (TEAD) factors. Expression of TONDU in Drosophila via UAS-GAL4 system substitutes for Vg in wing formation, establishing functional equivalence.","method":"Protein interaction assays, Drosophila UAS-GAL4 ectopic expression rescue experiment","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction assays plus in vivo genetic rescue in Drosophila, foundational paper replicated by later structural work","pmids":["10518497"],"is_preprint":false},{"year":2012,"finding":"Crystal structure of the Vgll1-TEAD4 complex shows that Vgll1 binds to TEAD4 at the same surface as YAP and TAZ, despite different primary sequence. The Vgll1-TEAD complex upregulates IGFBP-5 expression and promotes anchorage-independent cell proliferation.","method":"X-ray crystallography, luciferase reporter assay, soft-agar anchorage-independent growth assay","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional validation (reporter assay + proliferation assay) in a single rigorous study","pmids":["22632831"],"is_preprint":false},{"year":2014,"finding":"Vgll1-derived peptides bind to human TEAD4 with nanomolar affinity via a β-strand:loop:α-helix motif (the minimal Vgll binding site), despite lacking a key secondary structure element required for tight binding by YAP and TAZ. A difference between mouse and human Vgll1-derived peptides in TEAD binding was identified.","method":"Biophysical binding assays (peptide-TEAD4 interaction), mutagenesis-guided peptide analysis","journal":"Chembiochem : a European journal of chemical biology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biophysical assay defining minimal binding motif, single lab, single study","pmids":["24504694"],"is_preprint":false},{"year":2020,"finding":"TGF-β signaling promotes VGLL1 phosphorylation at serine 84 (S84) via the ERK/RSK2 kinase cascade. Phosphorylated RSK2 translocates to the nucleus and directly phosphorylates VGLL1 at S84. Phosphorylation at S84 is required for VGLL1-TEAD4 binding and subsequent transcriptional activation of MMP9. Mutation of S84 to alanine suppresses VGLL1-TEAD4 interaction and MMP9-mediated invasion and proliferation of gastric cancer cells.","method":"Site-directed mutagenesis, co-immunoprecipitation, kinase assay, luciferase reporter assay, invasion/proliferation assays","journal":"Biochimica et biophysica acta. Molecular cell research","confidence":"High","confidence_rationale":"Tier 1-2 / Moderate — site-directed mutagenesis combined with co-IP and functional assays, multiple orthogonal methods in single lab","pmids":["33069758"],"is_preprint":false},{"year":2020,"finding":"VGLL1 interacts with TEAD transcription factors via a conserved TONDU domain. Human VGLL1 and VGLL3 interact with TEAD via the TONDU motif alone, whereas Drosophila Vg and human VGLL2 require an additional Ω-loop structural element for TEAD binding. This structural difference reflects evolutionary divergence after vertebrate genome duplication.","method":"Structural analysis, binding assays comparing Vg/VGLL family members, mutagenesis of Ω-loop","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — structural and binding data for VGLL1 and VGLL3 vs. VGLL2/Vg, two orthogonal approaches, single lab","pmids":["33060790"],"is_preprint":false},{"year":2020,"finding":"VGLL1 binds to the HPV16 long control region (LCR) via its interaction with TEAD1, recruiting VGLL1/TEAD1 complexes to 11 TEAD1 target sites. Knockdown of VGLL1 and/or TEAD1 decreases HPV early gene expression in human cervical keratinocytes and cervical cancer cell lines. VGLL1 is required for growth of cervical cancer cells.","method":"siRNA knockdown, in vitro DNA pulldown assay, luciferase reporter assay, ChIP (in vivo LCR binding), cell proliferation assay","journal":"Journal of virology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (pulldown, ChIP, reporter, KD phenotype), single lab","pmids":["32132238"],"is_preprint":false},{"year":2024,"finding":"VGLL1 partners with TEAD4 to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C during human trophectoderm (TE) specification. VGLL1 is essential for cell fate determination and self-renewal in human trophectoderm-like cells (TELCs) and trophoblast stem cells (TSCs) derived from naïve pluripotent stem cells.","method":"CRISPR/KO of VGLL1, ChIP-seq for histone acetylation, ATAC-seq, co-immunoprecipitation with TEAD4/GATA3/TFAP2C, differentiation assays","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function with defined cellular phenotype, ChIP-seq, ATAC-seq, and protein interaction data in a single rigorous study","pmids":["38233381"],"is_preprint":false},{"year":2024,"finding":"VGLL1 stabilizes cytoplasmic TAZ independently of TEAD binding, promoting EGFR expression and increasing the frequency of CD44high/CD24low breast tumor-initiating cells. The TEAD-binding domain of TAZ is dispensable for this function, whereas nuclear expulsion of TAZ by VGLL1 represses AXL expression. VGLL1/TAZ also restricts surface expression of CD24.","method":"Co-immunoprecipitation, knockdown/overexpression, flow cytometry (CD44/CD24 surface expression), domain-deletion constructs, Western blot","journal":"Cellular signalling","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — co-IP plus functional assays, single lab, single study with multiple readouts","pmids":["38417636"],"is_preprint":false},{"year":2024,"finding":"Drug-induced epigenetic reprogramming (H3K27 acetylation changes) by selective ER degraders (e.g., fulvestrant) promotes VGLL1 expression. VGLL1, acting via TEAD transcription factors, drives transcription of proliferation genes including EGFR in ET-resistant breast cancer cells. Pharmacological disruption of the VGLL1-TEAD4 interaction inhibits VGLL1/TEAD-induced transcriptional programs and prevents growth of resistant cells.","method":"H3K27ac ChIP-seq, RNA-seq, pharmacological VGLL1-TEAD4 disruption, cell proliferation assays, EGFR inhibitor sensitization assay","journal":"Cancer research","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ChIP-seq, RNA-seq, and pharmacological intervention with defined phenotypic readouts, multiple orthogonal methods","pmids":["39356622"],"is_preprint":false},{"year":2024,"finding":"METTL3-mediated N6-methyladenosine (m6A) modification of VGLL1 mRNA, recognized by IGF2BP2, contributes to VGLL1 upregulation in ovarian cancer. VGLL1 directly interacts with TEAD4 and co-transcriptionally activates HMGA1, which further activates Wnt/β-catenin signaling to enhance metastasis via EMT. HMGA1 upregulation is essential for VGLL1-induced metastasis.","method":"m6A-seq/MeRIP, co-immunoprecipitation (VGLL1-TEAD4), rescue assays (HMGA1 overexpression), mouse models, cell invasion/proliferation assays","journal":"iScience","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — co-IP plus epitranscriptomic assay and rescue experiments, multiple methods, single lab","pmids":["38439973"],"is_preprint":false},{"year":2024,"finding":"ChIP-seq identified that VGLL1 binds chromatin at motifs for TEAD1-4, AP-1, and GATA6 across placental, pancreatic, and breast cancer cells, with ~3,000 shared target genes. Increased VGLL1 expression enhances cell invasion and proliferation, with transcriptional changes in invasion and proliferation pathway genes confirmed by RNA-seq.","method":"ChIP-seq, RNA-seq, cell invasion assay, cell proliferation assay","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP-seq and RNA-seq with functional assays, single lab, single study","pmids":["38912065"],"is_preprint":false},{"year":2025,"finding":"VGLL1 is expressed downstream of key trophectoderm transcription factors (GATA2/3, TFAP2A/C) but is essential for establishing full trophoblast identity. Mechanistically, VGLL1 upregulates EGFR and reinforces GATA3 expression through positive feedback, enhances canonical WNT signaling via direct regulation of WNT receptors and effectors, and directly regulates KDM6B (a histone demethylase removing H3K27me3), which facilitates activation of bivalent TE marker promoters.","method":"PSC-based BMP4 TE induction model, ATAC-seq, RNA-seq, ChIP-seq, VGLL1 loss-of-function, epistasis with GATA2/3 and TFAP2A/C","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Moderate — ATAC-seq, RNA-seq, ChIP-seq, and loss-of-function with defined cellular phenotype in multiple orthogonal approaches, single lab","pmids":["41284866"],"is_preprint":false},{"year":2024,"finding":"The TEAD-binding domain of VGLL1 (and VGLL2 and VGLL3) in vertebrates is defined by a conserved VxxHF (valine-x-x-histidine-phenylalanine) Tondu motif. Sequence conservation analysis of >2400 putative VGLL proteins reveals strong selective pressure to maintain one VGLL paralog with both a Tondu motif and an Ω-loop in vertebrates, while VGLL1 and VGLL3 lack the Ω-loop present in VGLL2.","method":"Sequence analysis of structural data, comparative biochemistry using available crystal structures","journal":"Archives of biochemistry and biophysics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — primarily computational/sequence analysis using existing structural data, no new experimental validation","pmids":["39182750"],"is_preprint":false},{"year":2022,"finding":"siRNA-mediated knockdown of VGLL1 in chicken granulosa cells causes decreased expression of BCL2, CCND1, and STAR, increased CASP3 expression, increased apoptosis, and reduced proliferation. This establishes VGLL1 as a promoter of cell proliferation and steroidogenesis and inhibitor of apoptosis in ovarian follicle granulosa cells.","method":"siRNA knockdown, RT-qPCR, flow cytometry (apoptosis), proliferation assay","journal":"Theriogenology","confidence":"Medium","confidence_rationale":"Tier 2-3 / Weak — siRNA KD with defined phenotypic readout in a chicken ortholog model, single lab, single study","pmids":["35074718"],"is_preprint":false}],"current_model":"VGLL1 is a transcriptional co-activator that binds TEAD transcription factors (TEAD1-4) via a conserved Tondu (VxxHF) motif, occupying the same TEAD surface as YAP/TAZ; its activity is regulated by phosphorylation at S84 by RSK2 downstream of TGF-β/ERK signaling, which enables TEAD4 binding and transcriptional activation of targets including MMP9, EGFR, IGFBP-5, and HMGA1; in trophectoderm development VGLL1 partners with TEAD4, GATA3, and TFAP2C to remodel chromatin (via histone acetylation and KDM6B-mediated H3K27me3 removal) and integrates HIPPO, BMP, and WNT signaling to establish trophoblast identity, while in cancer contexts it drives invasion, proliferation, and therapy resistance through TEAD-dependent transcriptional programs."},"narrative":{"mechanistic_narrative":"VGLL1 is a transcriptional co-activator that partners with TEAD transcription factors to control programs of cell proliferation, invasion, and lineage specification [PMID:22632831, PMID:38233381]. It engages TEAD via a conserved Tondu (VxxHF) motif and binds the same TEAD surface used by the Hippo effectors YAP and TAZ, despite lacking the Ω-loop element required for high-affinity binding by VGLL2 and Drosophila Vestigial; this Tondu-only mode of binding is functionally equivalent to Vestigial, as human VGLL1 substitutes for Vg in Drosophila wing formation [PMID:10518497, PMID:22632831, PMID:33060790]. VGLL1-TEAD complexes activate targets including IGFBP-5, MMP9, EGFR, HMGA1, and HPV early genes, and this output is gated by TGF-β/ERK/RSK2-driven phosphorylation of VGLL1 at serine 84, which is required for TEAD4 binding and downstream invasion and proliferation [PMID:22632831, PMID:33069758, PMID:32132238, PMID:39356622, PMID:38439973]. In human trophectoderm specification, VGLL1 acts downstream of GATA2/3 and TFAP2A/C yet is essential for full trophoblast identity, remodeling chromatin accessibility through histone acetylation with TEAD4, GATA3, and TFAP2C, reinforcing GATA3 and WNT signaling, and directly inducing the H3K27me3 demethylase KDM6B to activate bivalent trophoblast promoters [PMID:38233381, PMID:41284866]. Across placental, pancreatic, and cancer cells VGLL1 binds chromatin at TEAD, AP-1, and GATA motifs to drive shared invasion and proliferation programs, and it is recurrently upregulated in cancer through epigenetic and epitranscriptomic mechanisms—H3K27ac reprogramming under endocrine therapy and METTL3/IGF2BP2-mediated m6A modification—making the VGLL1-TEAD interface a pharmacological target in therapy-resistant tumors [PMID:39356622, PMID:38439973, PMID:38912065].","teleology":[{"year":1999,"claim":"Established that human VGLL1 (TONDU) is a functional TEAD partner by showing it carries a Vestigial-homologous domain that interacts with all mammalian TEAD factors and can replace Vestigial in vivo.","evidence":"Protein interaction assays plus Drosophila UAS-GAL4 ectopic rescue of wing formation","pmids":["10518497"],"confidence":"High","gaps":["Did not define the structural basis of the interaction","No mammalian transcriptional target identified"]},{"year":2012,"claim":"Resolved how VGLL1 docks onto TEAD and linked the interaction to a proliferative output, showing it occupies the same TEAD4 surface as YAP/TAZ and drives IGFBP-5 expression and anchorage-independent growth.","evidence":"X-ray crystallography of the Vgll1-TEAD4 complex with luciferase reporter and soft-agar assays","pmids":["22632831"],"confidence":"High","gaps":["Did not address regulation of VGLL1 activity","Cancer relevance in vivo not tested"]},{"year":2014,"claim":"Defined the minimal VGLL1 TEAD-binding motif, showing nanomolar binding via a β-strand:loop:α-helix element despite lacking a secondary structure required by YAP/TAZ.","evidence":"Biophysical peptide-TEAD4 binding assays with mutagenesis-guided analysis","pmids":["24504694"],"confidence":"Medium","gaps":["In vitro peptide binding only","Functional consequence of mouse-human difference not established"]},{"year":2020,"claim":"Identified the signaling input that switches VGLL1 on, showing TGF-β/ERK/RSK2 phosphorylates VGLL1 at S84 to enable TEAD4 binding and MMP9-driven invasion in gastric cancer.","evidence":"Site-directed mutagenesis, co-IP, kinase assay, reporter and invasion/proliferation assays","pmids":["33069758"],"confidence":"High","gaps":["Whether S84 phosphorylation regulates other targets unknown","Phosphatase counter-regulation not defined"]},{"year":2020,"claim":"Clarified the evolutionary and structural logic of VGLL-TEAD binding, showing VGLL1 and VGLL3 bind TEAD via the Tondu motif alone whereas VGLL2 and Vg require an additional Ω-loop.","evidence":"Structural and binding assays comparing VGLL family members with Ω-loop mutagenesis","pmids":["33060790"],"confidence":"Medium","gaps":["Functional consequence of Tondu-only binding for target selection unresolved"]},{"year":2020,"claim":"Extended VGLL1 function to viral oncogenesis, showing VGLL1/TEAD1 occupies the HPV16 LCR to drive early gene expression and cervical cancer cell growth.","evidence":"siRNA knockdown, DNA pulldown, ChIP, reporter and proliferation assays in cervical keratinocytes/cancer cells","pmids":["32132238"],"confidence":"High","gaps":["Whether VGLL1 acts on host as well as viral promoters in this context not detailed"]},{"year":2024,"claim":"Defined VGLL1 as an essential chromatin remodeler in human trophectoderm, cooperating with TEAD4, GATA3, and TFAP2C to control accessibility and self-renewal.","evidence":"CRISPR KO, ChIP-seq for histone acetylation, ATAC-seq, co-IP, and differentiation assays in TELCs/TSCs","pmids":["38233381"],"confidence":"High","gaps":["Direct target genes downstream of chromatin remodeling not fully enumerated"]},{"year":2024,"claim":"Revealed a TEAD-independent VGLL1 function, showing cytoplasmic TAZ stabilization that promotes EGFR and tumor-initiating cell frequency while repressing AXL and CD24.","evidence":"Co-IP, knockdown/overexpression, domain-deletion constructs, flow cytometry, Western blot","pmids":["38417636"],"confidence":"Medium","gaps":["Single lab, single study","Mechanism of TAZ nuclear expulsion not resolved"]},{"year":2024,"claim":"Connected VGLL1 to endocrine therapy resistance, showing ER-degrader-induced H3K27ac reprogramming upregulates VGLL1 to drive TEAD-dependent EGFR transcription, with the VGLL1-TEAD4 interface as a druggable node.","evidence":"H3K27ac ChIP-seq, RNA-seq, pharmacological VGLL1-TEAD4 disruption, proliferation and EGFR inhibitor assays","pmids":["39356622"],"confidence":"High","gaps":["In vivo efficacy of interface disruption not established here"]},{"year":2024,"claim":"Defined an epitranscriptomic route to VGLL1 overexpression and its metastatic effector, showing METTL3/IGF2BP2 m6A modification raises VGLL1, which with TEAD4 activates HMGA1 to drive Wnt/EMT metastasis.","evidence":"MeRIP/m6A-seq, co-IP, HMGA1 rescue, mouse models, invasion/proliferation assays","pmids":["38439973"],"confidence":"Medium","gaps":["Single lab study","Whether HMGA1 is a direct VGLL1/TEAD target promoter not fully resolved"]},{"year":2024,"claim":"Mapped the genome-wide VGLL1 chromatin binding landscape, showing TEAD, AP-1, and GATA6 motif occupancy and ~3,000 shared targets across placental and cancer cell types driving invasion/proliferation.","evidence":"ChIP-seq, RNA-seq, invasion and proliferation assays","pmids":["38912065"],"confidence":"Medium","gaps":["Direct vs indirect target distinction limited","Single study"]},{"year":2025,"claim":"Positioned VGLL1 hierarchically in trophectoderm, showing it acts downstream of GATA2/3 and TFAP2A/C yet is required for full trophoblast identity via EGFR/GATA3 feedback, WNT regulation, and direct induction of KDM6B-mediated H3K27me3 removal.","evidence":"PSC BMP4 TE induction, ATAC-seq, RNA-seq, ChIP-seq, loss-of-function, epistasis","pmids":["41284866"],"confidence":"High","gaps":["Mechanism of KDM6B recruitment by VGLL1 not detailed"]},{"year":null,"claim":"How VGLL1 selects between TEAD-dependent transcriptional activation and TEAD-independent TAZ stabilization, and what determines its context-specific target gene repertoire, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model integrating phosphorylation, partner availability, and chromatin context","TEAD-independent mechanism rests on a single study"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,5,6,11]},{"term_id":"GO:0003677","term_label":"DNA binding","supporting_discovery_ids":[5,10]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[1,6,7]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[3,5,6,10]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[7]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[1,5,6,10,11]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[6,11]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[3,5,8,9]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[3,7,9,11]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[6,11]}],"complexes":["VGLL1-TEAD4 complex"],"partners":["TEAD4","TEAD1","GATA3","TFAP2C","TAZ","RSK2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q99990","full_name":"Transcription cofactor vestigial-like protein 1","aliases":["Protein TONDU"],"length_aa":258,"mass_kda":28.7,"function":"May act as a specific coactivator for the mammalian TEFs","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q99990/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VGLL1","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/VGLL1","total_profiled":1310},"omim":[{"mim_id":"609979","title":"VESTIGIAL-LIKE 2; VGLL2","url":"https://www.omim.org/entry/609979"},{"mim_id":"300583","title":"VESTIGIAL-LIKE 1; VGLL1","url":"https://www.omim.org/entry/300583"},{"mim_id":"189967","title":"TEA DOMAIN FAMILY MEMBER 1; TEAD1","url":"https://www.omim.org/entry/189967"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"placenta","ntpm":191.5}],"url":"https://www.proteinatlas.org/search/VGLL1"},"hgnc":{"alias_symbol":["TONDU","TDU"],"prev_symbol":[]},"alphafold":{"accession":"Q99990","domains":[{"cath_id":"-","chopping":"16-51","consensus_level":"medium","plddt":94.7097,"start":16,"end":51}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99990","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q99990-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q99990-F1-predicted_aligned_error_v6.png","plddt_mean":57.34},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VGLL1","jax_strain_url":"https://www.jax.org/strain/search?query=VGLL1"},"sequence":{"accession":"Q99990","fasta_url":"https://rest.uniprot.org/uniprotkb/Q99990.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q99990/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q99990"}},"corpus_meta":[{"pmid":"22632831","id":"PMC_22632831","title":"Structural and functional similarity between the Vgll1-TEAD and the YAP-TEAD complexes.","date":"2012","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/22632831","citation_count":146,"is_preprint":false},{"pmid":"10518497","id":"PMC_10518497","title":"TONDU (TDU), a novel human protein related to the product of vestigial (vg) gene of Drosophila melanogaster interacts with vertebrate TEF factors and substitutes for Vg function in wing formation.","date":"1999","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/10518497","citation_count":120,"is_preprint":false},{"pmid":"24891455","id":"PMC_24891455","title":"VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer.","date":"2014","source":"Endocrine-related cancer","url":"https://pubmed.ncbi.nlm.nih.gov/24891455","citation_count":55,"is_preprint":false},{"pmid":"24504694","id":"PMC_24504694","title":"The surprising features of the TEAD4-Vgll1 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medicine","url":"https://pubmed.ncbi.nlm.nih.gov/41540017","citation_count":1,"is_preprint":false},{"pmid":"40300335","id":"PMC_40300335","title":"Vestigial-like family member 1 (VGLL1): An emerging candidate in tumor progression.","date":"2025","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/40300335","citation_count":0,"is_preprint":false},{"pmid":"40630581","id":"PMC_40630581","title":"Distinguishing benign from pathogenic duplications involving GPR101 and VGLL1-adjacent enhancers in the clinical setting with the bioinformatic tool POSTRE.","date":"2025","source":"medRxiv : the preprint server for health sciences","url":"https://pubmed.ncbi.nlm.nih.gov/40630581","citation_count":0,"is_preprint":false},{"pmid":"41522855","id":"PMC_41522855","title":"Central nervous system schwannoma, VGLL-fused (EWSR1::VGLL1 fusion) with neuroblastoma-like cell dense areas in the frontal lobe of a young man with schwannomatosis due to a germline 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Expression of TONDU in Drosophila via UAS-GAL4 system substitutes for Vg in wing formation, establishing functional equivalence.\",\n      \"method\": \"Protein interaction assays, Drosophila UAS-GAL4 ectopic expression rescue experiment\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction assays plus in vivo genetic rescue in Drosophila, foundational paper replicated by later structural work\",\n      \"pmids\": [\"10518497\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Crystal structure of the Vgll1-TEAD4 complex shows that Vgll1 binds to TEAD4 at the same surface as YAP and TAZ, despite different primary sequence. The Vgll1-TEAD complex upregulates IGFBP-5 expression and promotes anchorage-independent cell proliferation.\",\n      \"method\": \"X-ray crystallography, luciferase reporter assay, soft-agar anchorage-independent growth assay\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional validation (reporter assay + proliferation assay) in a single rigorous study\",\n      \"pmids\": [\"22632831\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Vgll1-derived peptides bind to human TEAD4 with nanomolar affinity via a β-strand:loop:α-helix motif (the minimal Vgll binding site), despite lacking a key secondary structure element required for tight binding by YAP and TAZ. A difference between mouse and human Vgll1-derived peptides in TEAD binding was identified.\",\n      \"method\": \"Biophysical binding assays (peptide-TEAD4 interaction), mutagenesis-guided peptide analysis\",\n      \"journal\": \"Chembiochem : a European journal of chemical biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biophysical assay defining minimal binding motif, single lab, single study\",\n      \"pmids\": [\"24504694\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TGF-β signaling promotes VGLL1 phosphorylation at serine 84 (S84) via the ERK/RSK2 kinase cascade. Phosphorylated RSK2 translocates to the nucleus and directly phosphorylates VGLL1 at S84. Phosphorylation at S84 is required for VGLL1-TEAD4 binding and subsequent transcriptional activation of MMP9. Mutation of S84 to alanine suppresses VGLL1-TEAD4 interaction and MMP9-mediated invasion and proliferation of gastric cancer cells.\",\n      \"method\": \"Site-directed mutagenesis, co-immunoprecipitation, kinase assay, luciferase reporter assay, invasion/proliferation assays\",\n      \"journal\": \"Biochimica et biophysica acta. Molecular cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — site-directed mutagenesis combined with co-IP and functional assays, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"33069758\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"VGLL1 interacts with TEAD transcription factors via a conserved TONDU domain. Human VGLL1 and VGLL3 interact with TEAD via the TONDU motif alone, whereas Drosophila Vg and human VGLL2 require an additional Ω-loop structural element for TEAD binding. This structural difference reflects evolutionary divergence after vertebrate genome duplication.\",\n      \"method\": \"Structural analysis, binding assays comparing Vg/VGLL family members, mutagenesis of Ω-loop\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — structural and binding data for VGLL1 and VGLL3 vs. VGLL2/Vg, two orthogonal approaches, single lab\",\n      \"pmids\": [\"33060790\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"VGLL1 binds to the HPV16 long control region (LCR) via its interaction with TEAD1, recruiting VGLL1/TEAD1 complexes to 11 TEAD1 target sites. Knockdown of VGLL1 and/or TEAD1 decreases HPV early gene expression in human cervical keratinocytes and cervical cancer cell lines. VGLL1 is required for growth of cervical cancer cells.\",\n      \"method\": \"siRNA knockdown, in vitro DNA pulldown assay, luciferase reporter assay, ChIP (in vivo LCR binding), cell proliferation assay\",\n      \"journal\": \"Journal of virology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (pulldown, ChIP, reporter, KD phenotype), single lab\",\n      \"pmids\": [\"32132238\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"VGLL1 partners with TEAD4 to regulate chromatin accessibility at target gene loci through histone acetylation and acts in cooperation with GATA3 and TFAP2C during human trophectoderm (TE) specification. VGLL1 is essential for cell fate determination and self-renewal in human trophectoderm-like cells (TELCs) and trophoblast stem cells (TSCs) derived from naïve pluripotent stem cells.\",\n      \"method\": \"CRISPR/KO of VGLL1, ChIP-seq for histone acetylation, ATAC-seq, co-immunoprecipitation with TEAD4/GATA3/TFAP2C, differentiation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function with defined cellular phenotype, ChIP-seq, ATAC-seq, and protein interaction data in a single rigorous study\",\n      \"pmids\": [\"38233381\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"VGLL1 stabilizes cytoplasmic TAZ independently of TEAD binding, promoting EGFR expression and increasing the frequency of CD44high/CD24low breast tumor-initiating cells. The TEAD-binding domain of TAZ is dispensable for this function, whereas nuclear expulsion of TAZ by VGLL1 represses AXL expression. VGLL1/TAZ also restricts surface expression of CD24.\",\n      \"method\": \"Co-immunoprecipitation, knockdown/overexpression, flow cytometry (CD44/CD24 surface expression), domain-deletion constructs, Western blot\",\n      \"journal\": \"Cellular signalling\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — co-IP plus functional assays, single lab, single study with multiple readouts\",\n      \"pmids\": [\"38417636\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Drug-induced epigenetic reprogramming (H3K27 acetylation changes) by selective ER degraders (e.g., fulvestrant) promotes VGLL1 expression. VGLL1, acting via TEAD transcription factors, drives transcription of proliferation genes including EGFR in ET-resistant breast cancer cells. Pharmacological disruption of the VGLL1-TEAD4 interaction inhibits VGLL1/TEAD-induced transcriptional programs and prevents growth of resistant cells.\",\n      \"method\": \"H3K27ac ChIP-seq, RNA-seq, pharmacological VGLL1-TEAD4 disruption, cell proliferation assays, EGFR inhibitor sensitization assay\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP-seq, RNA-seq, and pharmacological intervention with defined phenotypic readouts, multiple orthogonal methods\",\n      \"pmids\": [\"39356622\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"METTL3-mediated N6-methyladenosine (m6A) modification of VGLL1 mRNA, recognized by IGF2BP2, contributes to VGLL1 upregulation in ovarian cancer. VGLL1 directly interacts with TEAD4 and co-transcriptionally activates HMGA1, which further activates Wnt/β-catenin signaling to enhance metastasis via EMT. HMGA1 upregulation is essential for VGLL1-induced metastasis.\",\n      \"method\": \"m6A-seq/MeRIP, co-immunoprecipitation (VGLL1-TEAD4), rescue assays (HMGA1 overexpression), mouse models, cell invasion/proliferation assays\",\n      \"journal\": \"iScience\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — co-IP plus epitranscriptomic assay and rescue experiments, multiple methods, single lab\",\n      \"pmids\": [\"38439973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ChIP-seq identified that VGLL1 binds chromatin at motifs for TEAD1-4, AP-1, and GATA6 across placental, pancreatic, and breast cancer cells, with ~3,000 shared target genes. Increased VGLL1 expression enhances cell invasion and proliferation, with transcriptional changes in invasion and proliferation pathway genes confirmed by RNA-seq.\",\n      \"method\": \"ChIP-seq, RNA-seq, cell invasion assay, cell proliferation assay\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP-seq and RNA-seq with functional assays, single lab, single study\",\n      \"pmids\": [\"38912065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VGLL1 is expressed downstream of key trophectoderm transcription factors (GATA2/3, TFAP2A/C) but is essential for establishing full trophoblast identity. Mechanistically, VGLL1 upregulates EGFR and reinforces GATA3 expression through positive feedback, enhances canonical WNT signaling via direct regulation of WNT receptors and effectors, and directly regulates KDM6B (a histone demethylase removing H3K27me3), which facilitates activation of bivalent TE marker promoters.\",\n      \"method\": \"PSC-based BMP4 TE induction model, ATAC-seq, RNA-seq, ChIP-seq, VGLL1 loss-of-function, epistasis with GATA2/3 and TFAP2A/C\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ATAC-seq, RNA-seq, ChIP-seq, and loss-of-function with defined cellular phenotype in multiple orthogonal approaches, single lab\",\n      \"pmids\": [\"41284866\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"The TEAD-binding domain of VGLL1 (and VGLL2 and VGLL3) in vertebrates is defined by a conserved VxxHF (valine-x-x-histidine-phenylalanine) Tondu motif. Sequence conservation analysis of >2400 putative VGLL proteins reveals strong selective pressure to maintain one VGLL paralog with both a Tondu motif and an Ω-loop in vertebrates, while VGLL1 and VGLL3 lack the Ω-loop present in VGLL2.\",\n      \"method\": \"Sequence analysis of structural data, comparative biochemistry using available crystal structures\",\n      \"journal\": \"Archives of biochemistry and biophysics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — primarily computational/sequence analysis using existing structural data, no new experimental validation\",\n      \"pmids\": [\"39182750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"siRNA-mediated knockdown of VGLL1 in chicken granulosa cells causes decreased expression of BCL2, CCND1, and STAR, increased CASP3 expression, increased apoptosis, and reduced proliferation. This establishes VGLL1 as a promoter of cell proliferation and steroidogenesis and inhibitor of apoptosis in ovarian follicle granulosa cells.\",\n      \"method\": \"siRNA knockdown, RT-qPCR, flow cytometry (apoptosis), proliferation assay\",\n      \"journal\": \"Theriogenology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Weak — siRNA KD with defined phenotypic readout in a chicken ortholog model, single lab, single study\",\n      \"pmids\": [\"35074718\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VGLL1 is a transcriptional co-activator that binds TEAD transcription factors (TEAD1-4) via a conserved Tondu (VxxHF) motif, occupying the same TEAD surface as YAP/TAZ; its activity is regulated by phosphorylation at S84 by RSK2 downstream of TGF-β/ERK signaling, which enables TEAD4 binding and transcriptional activation of targets including MMP9, EGFR, IGFBP-5, and HMGA1; in trophectoderm development VGLL1 partners with TEAD4, GATA3, and TFAP2C to remodel chromatin (via histone acetylation and KDM6B-mediated H3K27me3 removal) and integrates HIPPO, BMP, and WNT signaling to establish trophoblast identity, while in cancer contexts it drives invasion, proliferation, and therapy resistance through TEAD-dependent transcriptional programs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"VGLL1 is a transcriptional co-activator that partners with TEAD transcription factors to control programs of cell proliferation, invasion, and lineage specification [#1, #6]. It engages TEAD via a conserved Tondu (VxxHF) motif and binds the same TEAD surface used by the Hippo effectors YAP and TAZ, despite lacking the Ω-loop element required for high-affinity binding by VGLL2 and Drosophila Vestigial; this Tondu-only mode of binding is functionally equivalent to Vestigial, as human VGLL1 substitutes for Vg in Drosophila wing formation [#0, #1, #4]. VGLL1-TEAD complexes activate targets including IGFBP-5, MMP9, EGFR, HMGA1, and HPV early genes, and this output is gated by TGF-β/ERK/RSK2-driven phosphorylation of VGLL1 at serine 84, which is required for TEAD4 binding and downstream invasion and proliferation [#1, #3, #5, #8, #9]. In human trophectoderm specification, VGLL1 acts downstream of GATA2/3 and TFAP2A/C yet is essential for full trophoblast identity, remodeling chromatin accessibility through histone acetylation with TEAD4, GATA3, and TFAP2C, reinforcing GATA3 and WNT signaling, and directly inducing the H3K27me3 demethylase KDM6B to activate bivalent trophoblast promoters [#6, #11]. Across placental, pancreatic, and cancer cells VGLL1 binds chromatin at TEAD, AP-1, and GATA motifs to drive shared invasion and proliferation programs, and it is recurrently upregulated in cancer through epigenetic and epitranscriptomic mechanisms—H3K27ac reprogramming under endocrine therapy and METTL3/IGF2BP2-mediated m6A modification—making the VGLL1-TEAD interface a pharmacological target in therapy-resistant tumors [#8, #9, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established that human VGLL1 (TONDU) is a functional TEAD partner by showing it carries a Vestigial-homologous domain that interacts with all mammalian TEAD factors and can replace Vestigial in vivo.\",\n      \"evidence\": \"Protein interaction assays plus Drosophila UAS-GAL4 ectopic rescue of wing formation\",\n      \"pmids\": [\"10518497\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the structural basis of the interaction\", \"No mammalian transcriptional target identified\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Resolved how VGLL1 docks onto TEAD and linked the interaction to a proliferative output, showing it occupies the same TEAD4 surface as YAP/TAZ and drives IGFBP-5 expression and anchorage-independent growth.\",\n      \"evidence\": \"X-ray crystallography of the Vgll1-TEAD4 complex with luciferase reporter and soft-agar assays\",\n      \"pmids\": [\"22632831\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address regulation of VGLL1 activity\", \"Cancer relevance in vivo not tested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Defined the minimal VGLL1 TEAD-binding motif, showing nanomolar binding via a β-strand:loop:α-helix element despite lacking a secondary structure required by YAP/TAZ.\",\n      \"evidence\": \"Biophysical peptide-TEAD4 binding assays with mutagenesis-guided analysis\",\n      \"pmids\": [\"24504694\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vitro peptide binding only\", \"Functional consequence of mouse-human difference not established\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified the signaling input that switches VGLL1 on, showing TGF-β/ERK/RSK2 phosphorylates VGLL1 at S84 to enable TEAD4 binding and MMP9-driven invasion in gastric cancer.\",\n      \"evidence\": \"Site-directed mutagenesis, co-IP, kinase assay, reporter and invasion/proliferation assays\",\n      \"pmids\": [\"33069758\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether S84 phosphorylation regulates other targets unknown\", \"Phosphatase counter-regulation not defined\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Clarified the evolutionary and structural logic of VGLL-TEAD binding, showing VGLL1 and VGLL3 bind TEAD via the Tondu motif alone whereas VGLL2 and Vg require an additional Ω-loop.\",\n      \"evidence\": \"Structural and binding assays comparing VGLL family members with Ω-loop mutagenesis\",\n      \"pmids\": [\"33060790\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of Tondu-only binding for target selection unresolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended VGLL1 function to viral oncogenesis, showing VGLL1/TEAD1 occupies the HPV16 LCR to drive early gene expression and cervical cancer cell growth.\",\n      \"evidence\": \"siRNA knockdown, DNA pulldown, ChIP, reporter and proliferation assays in cervical keratinocytes/cancer cells\",\n      \"pmids\": [\"32132238\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether VGLL1 acts on host as well as viral promoters in this context not detailed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined VGLL1 as an essential chromatin remodeler in human trophectoderm, cooperating with TEAD4, GATA3, and TFAP2C to control accessibility and self-renewal.\",\n      \"evidence\": \"CRISPR KO, ChIP-seq for histone acetylation, ATAC-seq, co-IP, and differentiation assays in TELCs/TSCs\",\n      \"pmids\": [\"38233381\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct target genes downstream of chromatin remodeling not fully enumerated\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Revealed a TEAD-independent VGLL1 function, showing cytoplasmic TAZ stabilization that promotes EGFR and tumor-initiating cell frequency while repressing AXL and CD24.\",\n      \"evidence\": \"Co-IP, knockdown/overexpression, domain-deletion constructs, flow cytometry, Western blot\",\n      \"pmids\": [\"38417636\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single study\", \"Mechanism of TAZ nuclear expulsion not resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected VGLL1 to endocrine therapy resistance, showing ER-degrader-induced H3K27ac reprogramming upregulates VGLL1 to drive TEAD-dependent EGFR transcription, with the VGLL1-TEAD4 interface as a druggable node.\",\n      \"evidence\": \"H3K27ac ChIP-seq, RNA-seq, pharmacological VGLL1-TEAD4 disruption, proliferation and EGFR inhibitor assays\",\n      \"pmids\": [\"39356622\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo efficacy of interface disruption not established here\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined an epitranscriptomic route to VGLL1 overexpression and its metastatic effector, showing METTL3/IGF2BP2 m6A modification raises VGLL1, which with TEAD4 activates HMGA1 to drive Wnt/EMT metastasis.\",\n      \"evidence\": \"MeRIP/m6A-seq, co-IP, HMGA1 rescue, mouse models, invasion/proliferation assays\",\n      \"pmids\": [\"38439973\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab study\", \"Whether HMGA1 is a direct VGLL1/TEAD target promoter not fully resolved\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Mapped the genome-wide VGLL1 chromatin binding landscape, showing TEAD, AP-1, and GATA6 motif occupancy and ~3,000 shared targets across placental and cancer cell types driving invasion/proliferation.\",\n      \"evidence\": \"ChIP-seq, RNA-seq, invasion and proliferation assays\",\n      \"pmids\": [\"38912065\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs indirect target distinction limited\", \"Single study\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Positioned VGLL1 hierarchically in trophectoderm, showing it acts downstream of GATA2/3 and TFAP2A/C yet is required for full trophoblast identity via EGFR/GATA3 feedback, WNT regulation, and direct induction of KDM6B-mediated H3K27me3 removal.\",\n      \"evidence\": \"PSC BMP4 TE induction, ATAC-seq, RNA-seq, ChIP-seq, loss-of-function, epistasis\",\n      \"pmids\": [\"41284866\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of KDM6B recruitment by VGLL1 not detailed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How VGLL1 selects between TEAD-dependent transcriptional activation and TEAD-independent TAZ stabilization, and what determines its context-specific target gene repertoire, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model integrating phosphorylation, partner availability, and chromatin context\", \"TEAD-independent mechanism rests on a single study\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 5, 6, 11]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [5, 10]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [1, 6, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [3, 5, 6, 10]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [1, 5, 6, 10, 11]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [6, 11]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [3, 5, 8, 9]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3, 7, 9, 11]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [6, 11]}\n    ],\n    \"complexes\": [\"VGLL1-TEAD4 complex\"],\n    \"partners\": [\"TEAD4\", \"TEAD1\", \"GATA3\", \"TFAP2C\", \"TAZ\", \"RSK2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":5,"faith_total":5,"faith_pct":100.0}}