{"gene":"NELFB","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2009,"finding":"NELFB/COBRA1 is required for inner cell mass (ICM) integrity and early embryogenesis; knockout causes embryonic lethality at implantation. In mouse embryonic stem cells, COBRA1 depletion reduces colony formation, increases spontaneous differentiation, and leads to precocious expression of developmental regulators (e.g., Lef1). ChIP shows COBRA1 binds the Lef1 promoter and modulates promoter-bound RNA polymerase II abundance.","method":"Knockout mouse model, shRNA knockdown in ESCs, chromatin immunoprecipitation (ChIP)","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic KO with defined embryonic phenotype, ChIP linking COBRA1 to specific promoter occupancy and Pol II modulation, replicated across in vivo and in vitro systems","pmids":["19340312"],"is_preprint":false},{"year":2016,"finding":"Tissue-specific deletion of Cobra1 in mammary epithelium blocks ductal morphogenesis, alveologenesis, and lactogenesis. Additional loss of full-length Brca1 largely rescues these developmental defects and restores developmental transcription, demonstrating a DNA repair-independent antagonism between BRCA1 and COBRA1 in controlling the COBRA1-dependent transcription programme during mammary gland development.","method":"Conditional (tissue-specific) knockout mice, Brca1/Cobra1 double-knockout genetic epistasis, gene expression analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined tissue phenotype, double-KO genetic suppression establishing epistatic relationship, multiple orthogonal phenotypic readouts","pmids":["26941120"],"is_preprint":false},{"year":2013,"finding":"TrkC killer fragment (TrkC KF), generated by proteolytic cleavage of the dependence receptor TrkC in the absence of NT-3, physically interacts with COBRA1/NELFB. COBRA1 is required for TrkC-induced apoptosis; it shuttles TrkC KF to the mitochondria, where it promotes Bax activation, cytochrome c release, and apoptosome-dependent apoptosis.","method":"Co-immunoprecipitation, siRNA knockdown, subcellular fractionation/localization, apoptosis assays (cytochrome c release, Bax activation), in vivo chick neural tube NT-3 silencing","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP identifying TrkC KF as binding partner, functional rescue (Cobra1 silencing rescues NT-3 knockdown-induced cell death in vivo), multiple orthogonal mechanistic readouts","pmids":["24034695"],"is_preprint":false},{"year":2004,"finding":"COBRA1 physically interacts with AP-1 family members c-Jun and c-Fos; the middle region of COBRA1 binds c-Fos. Ectopic expression of COBRA1 inhibits AP-1 transcriptional activity in a dose-dependent manner, and the c-Fos binding region of COBRA1 is required for this inhibition.","method":"Co-immunoprecipitation, reporter gene assays (transfection), siRNA knockdown, domain-deletion mapping","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP with domain mapping and functional reporter assay, single lab with two orthogonal methods","pmids":["15530430"],"is_preprint":false},{"year":2004,"finding":"COBRA1 localizes to the nucleus in human breast cancer cells and co-immunoprecipitates with endogenous BRCA1, confirming a physical interaction between the two proteins in a cellular context.","method":"Immunofluorescence, co-immunoprecipitation with endogenous proteins","journal":"IUBMB life","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — immunofluorescence localization plus endogenous Co-IP, consistent with prior findings, single lab","pmids":["15185750"],"is_preprint":false},{"year":2013,"finding":"NELFB attenuates glucocorticoid receptor (GR)-mediated gene induction, reduces partial agonist activity of an antagonist, and increases the EC50 of an agonist. NELFB diminishes GR recruitment to promoter regions (by ChIP). NELFB and NELF-A each act independently as competitive decelerators at steps after GR action and before/at reporter gene activity. A conserved protein motif shared by NELF-A and NELF-B is required for full modulatory activity of both subunits.","method":"Stable shRNA knockdown, ChIP, competition assay (new assay design), mutagenesis of conserved motif, reporter gene assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP with endogenous promoters, mutagenesis, and functional assays in a single lab with multiple orthogonal methods","pmids":["24097989"],"is_preprint":false},{"year":2023,"finding":"Crystal structure of the human NELF-B/C/E ternary complex was solved at high resolution, revealing detailed inter-subunit interaction interfaces and identifying residues important for the association between NELF-B and NELF-E.","method":"X-ray crystallography (crystal structure determination)","journal":"Biochemical and biophysical research communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — high-resolution crystal structure with identification of key interfacial residues, single lab but Tier 1 method","pmids":["37591184"],"is_preprint":false},{"year":2023,"finding":"NELFB function in cell proliferation can be uncoupled from its role in nuclear Pol II pausing. NELFB mutants sequestered in the cytoplasm still support cell proliferation and part of the NELFB-dependent transcriptome. Cytoplasmic NELFB physically and functionally interacts with prosurvival signaling kinases, most notably PI3K/AKT. Ectopic expression of membrane-tethered PI3K/AKT partially bypasses the role of NELFB in cell proliferation but not Pol II occupancy.","method":"Separation-of-function mutagenesis (nuclear exclusion mutations), co-immunoprecipitation, ectopic expression of membrane-tethered PI3K/AKT, Pol II ChIP, cell proliferation assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — separation-of-function mutations with reciprocal Co-IP identifying PI3K/AKT as cytoplasmic interactor, orthogonal rescue experiment with membrane-tethered PI3K/AKT, multiple mechanistic readouts in one study","pmids":["37717699"],"is_preprint":false},{"year":2025,"finding":"Deletion of Nelfb from preadipocyte lineages in mice causes failure of dermal white adipose tissue (dWAT) and other fat depot formation, perinatal lethality, and reduced expression of adipogenic genes (Pparg, Cebpa, Krox20, Stat3). Nelfb promotes open chromatin structure and stabilizes RNA Pol II binding at these gene loci. Retroviral expression of Pparg in Nelfb-depleted cells restored adipocyte differentiation; treatment of Nelfb-deleted mice with the PPARγ agonist rosiglitazone allowed dWAT formation and prolonged lifespan.","method":"Conditional knockout mouse (preadipocyte-specific), chromatin accessibility assays, Pol II ChIP, retroviral rescue (Pparg), pharmacological rescue (rosiglitazone), cell differentiation assays","journal":"Development (Cambridge, England)","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional KO with defined developmental phenotype, ChIP linking NELFB to Pol II occupancy at specific loci, orthogonal genetic and pharmacological rescue experiments","pmids":["40960263"],"is_preprint":false},{"year":2018,"finding":"The genetic interaction between Brca1 and Cobra1 in mammary gland development is domain- and gene-specific: separation-of-function Brca1 mutations abrogating either its RING domain E3 ligase activity or BRCT domain phospho-recognition do not rescue Cobra1 KO mammary defects, and deletion of Palb2 also does not rescue these defects, unlike full-length Brca1 loss.","method":"Conditional double-knockout mice (Brca1 separation-of-function alleles × Cobra1 KO), mammary gland phenotypic analysis","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with separation-of-function alleles, clean in vivo phenotype, single lab","pmids":["29426838"],"is_preprint":false},{"year":2018,"finding":"COBRA1 positively influences androgen receptor (AR) target gene expression and promoter activity in prostate cancer cells; depletion decreases cell viability, proliferation, and anchorage-independent growth, while overexpression of COBRA1 allows AR-positive cells to survive under androgen-deprivation conditions.","method":"siRNA knockdown and ectopic overexpression, reporter/promoter activity assays, cell viability/proliferation assays, androgen deprivation experiments","journal":"International journal of molecular sciences","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — functional cell-based assays with KD and OE, promoter activity assays linking COBRA1 to AR target gene regulation, single lab","pmids":["30036938"],"is_preprint":false},{"year":2007,"finding":"Gene expression profiling after shRNA-mediated knockdown of COBRA1 and BRCA1 separately in breast cancer cells reveals a significant overlap in the sets of genes regulated by each factor, supporting shared gene regulatory pathways.","method":"shRNA knockdown, gene expression microarray","journal":"International journal of biological sciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — microarray after separate KDs without direct protein interaction or pathway placement experiments; overlap is correlative","pmids":["18071589"],"is_preprint":false}],"current_model":"NELFB (COBRA1/NELF-B) is a subunit of the four-component NELF complex that stabilizes promoter-proximal RNA Polymerase II pausing to regulate transcription elongation; it directly interacts with BRCA1 and antagonizes its transcriptional function during mammary gland development, binds AP-1 components (c-Jun/c-Fos) and the glucocorticoid receptor pathway to attenuate their transcriptional output, mediates TrkC dependence-receptor apoptosis by shuttling a proteolytic TrkC killer fragment to the mitochondria to activate Bax and cytochrome c release, and—separately from its nuclear Pol II pausing role—functions in the cytoplasm by interacting with PI3K/AKT to support cell proliferation, with structural studies defining the NELF-B/C/E ternary complex interface."},"narrative":{"mechanistic_narrative":"NELFB (COBRA1/NELF-B) is a subunit of the NELF complex that controls transcription elongation by stabilizing promoter-proximal RNA Polymerase II and shaping gene-specific output during development [PMID:19340312, PMID:40960263]. Through this activity it is essential for early embryogenesis and inner cell mass integrity, where it binds developmental promoters such as Lef1 and modulates promoter-bound Pol II to restrain precocious differentiation [PMID:19340312], and it drives lineage-specific programs in mammary epithelium [PMID:26941120] and in adipocyte differentiation, where it promotes open chromatin and stabilizes Pol II at adipogenic loci (Pparg, Cebpa) to enable adipose tissue formation [PMID:40960263]. In the nucleus NELFB functions as a transcriptional antagonist of multiple regulatory pathways: it physically interacts with BRCA1 in a DNA repair-independent manner and antagonizes BRCA1 control of the developmental transcription program [PMID:26941120, PMID:15185750], binds the AP-1 components c-Jun and c-Fos to inhibit AP-1 transcriptional activity [PMID:15530430], and attenuates glucocorticoid receptor-mediated gene induction by reducing GR promoter recruitment [PMID:24097989]. Structurally, NELFB forms a defined ternary interface with NELF-C and NELF-E [PMID:37591184]. Beyond transcription, NELFB has separable cytoplasmic functions: it shuttles the proteolytic TrkC killer fragment to mitochondria to trigger Bax activation, cytochrome c release, and apoptosis [PMID:24034695], and a cytoplasm-restricted pool interacts with PI3K/AKT to support cell proliferation independently of its Pol II pausing role [PMID:37717699].","teleology":[{"year":2004,"claim":"Establishing that COBRA1 is a nuclear partner and repressor of transcription factors gave it a defined regulatory role, first by showing it binds BRCA1 and inhibits AP-1.","evidence":"Endogenous co-immunoprecipitation and immunofluorescence (BRCA1) plus Co-IP, domain mapping, and reporter assays (c-Jun/c-Fos)","pmids":["15185750","15530430"],"confidence":"Medium","gaps":["Whether BRCA1 binding is direct versus complex-mediated was not resolved","The mechanism linking AP-1 binding to Pol II elongation control was not established"]},{"year":2007,"claim":"Comparing transcriptomes after COBRA1 versus BRCA1 knockdown asked whether the two factors share gene targets, supporting a common regulatory pathway.","evidence":"shRNA knockdown with gene expression microarray in breast cancer cells","pmids":["18071589"],"confidence":"Low","gaps":["Overlap is correlative without direct interaction or epistasis","Does not distinguish shared targets from independent regulation of the same genes"]},{"year":2009,"claim":"Knockout in mice and ESCs answered whether COBRA1 has a developmental requirement, showing it maintains the undifferentiated state by tuning Pol II at developmental promoters.","evidence":"Knockout mouse, shRNA in ESCs, and ChIP at the Lef1 promoter","pmids":["19340312"],"confidence":"High","gaps":["The full set of direct promoter targets was not mapped","How COBRA1 distinguishes genes to pause was not defined"]},{"year":2013,"claim":"Two studies expanded NELFB beyond Pol II pausing: one showed it executes dependence-receptor apoptosis, the other that it decelerates glucocorticoid receptor signaling.","evidence":"Co-IP, subcellular fractionation, apoptosis assays, and in vivo chick neural tube silencing (TrkC); shRNA, ChIP, competition assays, and motif mutagenesis (GR)","pmids":["24034695","24097989"],"confidence":"High","gaps":["The molecular signal triggering NELFB cytoplasmic-to-mitochondrial shuttling in TrkC apoptosis was not defined","Whether GR attenuation operates through the NELF pausing complex or independently was not separated"]},{"year":2016,"claim":"Conditional mammary knockout with Brca1 epistasis established that BRCA1 antagonizes the COBRA1 transcription program independently of DNA repair, defining their developmental relationship.","evidence":"Tissue-specific Cobra1 KO, Brca1/Cobra1 double-KO genetic suppression, and transcription analysis","pmids":["26941120"],"confidence":"High","gaps":["The biochemical mechanism by which BRCA1 counteracts COBRA1 was not defined","Which specific COBRA1 target genes drive the mammary phenotype was not pinpointed"]},{"year":2018,"claim":"Separation-of-function Brca1 alleles refined the antagonism, showing neither BRCA1 enzymatic nor phospho-recognition activity nor PALB2 rescues Cobra1 loss, narrowing the relevant BRCA1 function.","evidence":"Conditional double-KO mice with Brca1 RING and BRCT mutant alleles and Palb2 deletion","pmids":["29426838"],"confidence":"Medium","gaps":["The specific BRCA1 domain or activity that opposes COBRA1 remains unidentified","Single-lab in vivo result without biochemical reconstitution"]},{"year":2018,"claim":"Prostate cancer studies showed COBRA1 acts as a positive regulator of androgen receptor target genes, indicating its transcriptional effect is context- and factor-dependent rather than uniformly repressive.","evidence":"siRNA knockdown, overexpression, promoter reporter and proliferation assays under androgen deprivation","pmids":["30036938"],"confidence":"Medium","gaps":["Whether COBRA1 directly binds AR or its promoters was not shown","The mechanistic basis for positive versus negative transcriptional effects was not resolved"]},{"year":2023,"claim":"A crystal structure and a separation-of-function study together resolved how NELFB assembles into the NELF complex and uncoupled its cytoplasmic proliferative role from nuclear pausing.","evidence":"X-ray crystallography of the NELF-B/C/E ternary complex; nuclear-exclusion mutants, Co-IP, Pol II ChIP, and membrane-tethered PI3K/AKT rescue","pmids":["37591184","37717699"],"confidence":"High","gaps":["The cytoplasmic NELFB–PI3K/AKT interaction was not structurally defined","How a single protein partitions between nuclear pausing and cytoplasmic signaling functions was not fully explained"]},{"year":2025,"claim":"Preadipocyte-specific knockout established a NELFB requirement in adipogenesis, showing it enables open chromatin and Pol II loading at master adipogenic genes, with PPARγ acting downstream.","evidence":"Conditional KO mouse, chromatin accessibility and Pol II ChIP, retroviral Pparg rescue, and rosiglitazone pharmacological rescue","pmids":["40960263"],"confidence":"High","gaps":["How NELFB promotes chromatin opening mechanistically was not defined","Whether this depends on the canonical NELF complex was not tested"]},{"year":null,"claim":"It remains unresolved how NELFB selects specific genes for pausing versus activation across tissues, and what governs the partition between its nuclear transcriptional and cytoplasmic apoptotic/proliferative functions.","evidence":"","pmids":[],"confidence":"Low","gaps":["No unifying mechanism explains positive versus negative transcriptional outcomes","The trafficking signals controlling nuclear versus cytoplasmic NELFB are undefined","No direct biochemical link between the structural NELF interface and tissue-specific phenotypes"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[0,1,3,5,8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[0,4]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[7]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[0,1,5,8]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[0,1,8]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[2]}],"complexes":["NELF complex","NELF-B/C/E ternary complex"],"partners":["BRCA1","C-JUN","C-FOS","TRKC","NELFE","NELFC","PIK3CA","AKT1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WX92","full_name":"Negative elongation factor B","aliases":["Cofactor of BRCA1"],"length_aa":580,"mass_kda":65.7,"function":"Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:12612062). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:10199401). May be able to induce chromatin unfolding (PubMed:11739404). Essential for early embryogenesis; plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes (By similarity). Plays a key role in establishing the responsiveness of stem cells to developmental cues; facilitates plasticity and cell fate commitment in ESCs by establishing the appropriate expression level of signaling molecules (By similarity). Supports the transcription of genes involved in energy metabolism in cardiomyocytes; facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (By similarity) (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II (PubMed:23884411). In vitro, binds weakly to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1 (PubMed:23884411)","subcellular_location":"Nucleus","url":"https://www.uniprot.org/uniprotkb/Q8WX92/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NELFB","classification":"Common Essential","n_dependent_lines":1170,"n_total_lines":1208,"dependency_fraction":0.9685430463576159},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"INTS9","stoichiometry":10.0},{"gene":"POLR2B","stoichiometry":4.0},{"gene":"POLR2E","stoichiometry":0.2},{"gene":"POLR2F","stoichiometry":0.2},{"gene":"POLR2H","stoichiometry":0.2},{"gene":"POLR2I","stoichiometry":0.2},{"gene":"POLR2J","stoichiometry":0.2},{"gene":"POLR2K","stoichiometry":0.2},{"gene":"PPP2CA","stoichiometry":0.2},{"gene":"SSRP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NELFB","total_profiled":1310},"omim":[{"mim_id":"611180","title":"NEGATIVE ELONGATION FACTOR COMPLEX, MEMBER B; NELFB","url":"https://www.omim.org/entry/611180"},{"mim_id":"606026","title":"NEGATIVE ELONGATION FACTOR COMPLEX, MEMBER A; NELFA","url":"https://www.omim.org/entry/606026"},{"mim_id":"605297","title":"NEGATIVE ELONGATION FACTOR COMPLEX, MEMBER C/D; NELFCD","url":"https://www.omim.org/entry/605297"},{"mim_id":"154040","title":"NEGATIVE ELONGATION FACTOR COMPLEX, MEMBER E; NELFE","url":"https://www.omim.org/entry/154040"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nucleoplasm","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NELFB"},"hgnc":{"alias_symbol":["KIAA1182","NELF-B"],"prev_symbol":["COBRA1"]},"alphafold":{"accession":"Q8WX92","domains":[{"cath_id":"-","chopping":"1-37","consensus_level":"medium","plddt":78.9592,"start":1,"end":37},{"cath_id":"-","chopping":"42-149","consensus_level":"high","plddt":90.2576,"start":42,"end":149},{"cath_id":"-","chopping":"153-366","consensus_level":"medium","plddt":95.6712,"start":153,"end":366},{"cath_id":"1.25.40","chopping":"410-549","consensus_level":"high","plddt":94.638,"start":410,"end":549}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WX92","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WX92-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WX92-F1-predicted_aligned_error_v6.png","plddt_mean":89.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NELFB","jax_strain_url":"https://www.jax.org/strain/search?query=NELFB"},"sequence":{"accession":"Q8WX92","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WX92.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WX92/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WX92"}},"corpus_meta":[{"pmid":"19340312","id":"PMC_19340312","title":"Mouse cofactor of BRCA1 (Cobra1) is required for early embryogenesis.","date":"2009","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/19340312","citation_count":52,"is_preprint":false},{"pmid":"34705606","id":"PMC_34705606","title":"NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction.","date":"2021","source":"Cancer biology & therapy","url":"https://pubmed.ncbi.nlm.nih.gov/34705606","citation_count":32,"is_preprint":false},{"pmid":"26941120","id":"PMC_26941120","title":"Genetic suppression reveals DNA repair-independent antagonism between BRCA1 and COBRA1 in mammary gland development.","date":"2016","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/26941120","citation_count":22,"is_preprint":false},{"pmid":"24034695","id":"PMC_24034695","title":"The dependence receptor TrkC triggers mitochondria-dependent apoptosis upon Cobra-1 recruitment.","date":"2013","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/24034695","citation_count":20,"is_preprint":false},{"pmid":"18071589","id":"PMC_18071589","title":"Concerted transcriptional regulation by BRCA1 and COBRA1 in breast cancer cells.","date":"2007","source":"International journal of biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/18071589","citation_count":16,"is_preprint":false},{"pmid":"15530430","id":"PMC_15530430","title":"COBRA1 inhibits AP-1 transcriptional activity in transfected cells.","date":"2004","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/15530430","citation_count":12,"is_preprint":false},{"pmid":"24097989","id":"PMC_24097989","title":"A conserved protein motif is required for full modulatory activity of negative elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor-regulated gene induction properties.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/24097989","citation_count":11,"is_preprint":false},{"pmid":"28112367","id":"PMC_28112367","title":"Knockdown of COBRA1 decreases the proliferation and migration of hepatocellular carcinoma cells.","date":"2017","source":"Oncology reports","url":"https://pubmed.ncbi.nlm.nih.gov/28112367","citation_count":9,"is_preprint":false},{"pmid":"40960263","id":"PMC_40960263","title":"Nelfb promotes dermal white adipose tissue formation through RNA polymerase II-mediated adipogenic gene regulation.","date":"2025","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/40960263","citation_count":5,"is_preprint":false},{"pmid":"30036938","id":"PMC_30036938","title":"BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions.","date":"2018","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/30036938","citation_count":5,"is_preprint":false},{"pmid":"15185750","id":"PMC_15185750","title":"Characterization of COBRA1 in human breast cancer cell lines using a new polyclonal antibody against COBRA1.","date":"2004","source":"IUBMB life","url":"https://pubmed.ncbi.nlm.nih.gov/15185750","citation_count":5,"is_preprint":false},{"pmid":"37591184","id":"PMC_37591184","title":"Structural basis of the human negative elongation factor NELF-B/C/E ternary complex.","date":"2023","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/37591184","citation_count":5,"is_preprint":false},{"pmid":"29426838","id":"PMC_29426838","title":"Gene-Specific Genetic Complementation between Brca1 and Cobra1 During Mouse Mammary Gland Development.","date":"2018","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29426838","citation_count":4,"is_preprint":false},{"pmid":"10866379","id":"PMC_10866379","title":"COBRA-1, a rationally-designed epoxy-THF containing compound with potent tubulin depolymerizing activity as a novel anticancer agent.","date":"2000","source":"Bioorganic & medicinal chemistry letters","url":"https://pubmed.ncbi.nlm.nih.gov/10866379","citation_count":4,"is_preprint":false},{"pmid":"34539865","id":"PMC_34539865","title":"Role of NELF-B in supporting epithelial-mesenchymal transition and cell proliferation during hepatocellular carcinoma progression.","date":"2021","source":"Oncology letters","url":"https://pubmed.ncbi.nlm.nih.gov/34539865","citation_count":2,"is_preprint":false},{"pmid":"37717699","id":"PMC_37717699","title":"An essential signaling function of cytoplasmic NELFB is independent of RNA polymerase II pausing.","date":"2023","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/37717699","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.04.25.650599","title":"Identification of HIV Tat and NF-κB binding proteins associated with semen-derived extracellular vesicles","date":"2025-04-26","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.25.650599","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9400,"output_tokens":3170,"usd":0.037875,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10683,"output_tokens":3588,"usd":0.071557,"stage2_stop_reason":"end_turn"},"total_usd":0.109432,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2009,\n      \"finding\": \"NELFB/COBRA1 is required for inner cell mass (ICM) integrity and early embryogenesis; knockout causes embryonic lethality at implantation. In mouse embryonic stem cells, COBRA1 depletion reduces colony formation, increases spontaneous differentiation, and leads to precocious expression of developmental regulators (e.g., Lef1). ChIP shows COBRA1 binds the Lef1 promoter and modulates promoter-bound RNA polymerase II abundance.\",\n      \"method\": \"Knockout mouse model, shRNA knockdown in ESCs, chromatin immunoprecipitation (ChIP)\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic KO with defined embryonic phenotype, ChIP linking COBRA1 to specific promoter occupancy and Pol II modulation, replicated across in vivo and in vitro systems\",\n      \"pmids\": [\"19340312\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Tissue-specific deletion of Cobra1 in mammary epithelium blocks ductal morphogenesis, alveologenesis, and lactogenesis. Additional loss of full-length Brca1 largely rescues these developmental defects and restores developmental transcription, demonstrating a DNA repair-independent antagonism between BRCA1 and COBRA1 in controlling the COBRA1-dependent transcription programme during mammary gland development.\",\n      \"method\": \"Conditional (tissue-specific) knockout mice, Brca1/Cobra1 double-knockout genetic epistasis, gene expression analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined tissue phenotype, double-KO genetic suppression establishing epistatic relationship, multiple orthogonal phenotypic readouts\",\n      \"pmids\": [\"26941120\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TrkC killer fragment (TrkC KF), generated by proteolytic cleavage of the dependence receptor TrkC in the absence of NT-3, physically interacts with COBRA1/NELFB. COBRA1 is required for TrkC-induced apoptosis; it shuttles TrkC KF to the mitochondria, where it promotes Bax activation, cytochrome c release, and apoptosome-dependent apoptosis.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, subcellular fractionation/localization, apoptosis assays (cytochrome c release, Bax activation), in vivo chick neural tube NT-3 silencing\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP identifying TrkC KF as binding partner, functional rescue (Cobra1 silencing rescues NT-3 knockdown-induced cell death in vivo), multiple orthogonal mechanistic readouts\",\n      \"pmids\": [\"24034695\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"COBRA1 physically interacts with AP-1 family members c-Jun and c-Fos; the middle region of COBRA1 binds c-Fos. Ectopic expression of COBRA1 inhibits AP-1 transcriptional activity in a dose-dependent manner, and the c-Fos binding region of COBRA1 is required for this inhibition.\",\n      \"method\": \"Co-immunoprecipitation, reporter gene assays (transfection), siRNA knockdown, domain-deletion mapping\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP with domain mapping and functional reporter assay, single lab with two orthogonal methods\",\n      \"pmids\": [\"15530430\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"COBRA1 localizes to the nucleus in human breast cancer cells and co-immunoprecipitates with endogenous BRCA1, confirming a physical interaction between the two proteins in a cellular context.\",\n      \"method\": \"Immunofluorescence, co-immunoprecipitation with endogenous proteins\",\n      \"journal\": \"IUBMB life\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — immunofluorescence localization plus endogenous Co-IP, consistent with prior findings, single lab\",\n      \"pmids\": [\"15185750\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"NELFB attenuates glucocorticoid receptor (GR)-mediated gene induction, reduces partial agonist activity of an antagonist, and increases the EC50 of an agonist. NELFB diminishes GR recruitment to promoter regions (by ChIP). NELFB and NELF-A each act independently as competitive decelerators at steps after GR action and before/at reporter gene activity. A conserved protein motif shared by NELF-A and NELF-B is required for full modulatory activity of both subunits.\",\n      \"method\": \"Stable shRNA knockdown, ChIP, competition assay (new assay design), mutagenesis of conserved motif, reporter gene assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP with endogenous promoters, mutagenesis, and functional assays in a single lab with multiple orthogonal methods\",\n      \"pmids\": [\"24097989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Crystal structure of the human NELF-B/C/E ternary complex was solved at high resolution, revealing detailed inter-subunit interaction interfaces and identifying residues important for the association between NELF-B and NELF-E.\",\n      \"method\": \"X-ray crystallography (crystal structure determination)\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — high-resolution crystal structure with identification of key interfacial residues, single lab but Tier 1 method\",\n      \"pmids\": [\"37591184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"NELFB function in cell proliferation can be uncoupled from its role in nuclear Pol II pausing. NELFB mutants sequestered in the cytoplasm still support cell proliferation and part of the NELFB-dependent transcriptome. Cytoplasmic NELFB physically and functionally interacts with prosurvival signaling kinases, most notably PI3K/AKT. Ectopic expression of membrane-tethered PI3K/AKT partially bypasses the role of NELFB in cell proliferation but not Pol II occupancy.\",\n      \"method\": \"Separation-of-function mutagenesis (nuclear exclusion mutations), co-immunoprecipitation, ectopic expression of membrane-tethered PI3K/AKT, Pol II ChIP, cell proliferation assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — separation-of-function mutations with reciprocal Co-IP identifying PI3K/AKT as cytoplasmic interactor, orthogonal rescue experiment with membrane-tethered PI3K/AKT, multiple mechanistic readouts in one study\",\n      \"pmids\": [\"37717699\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Deletion of Nelfb from preadipocyte lineages in mice causes failure of dermal white adipose tissue (dWAT) and other fat depot formation, perinatal lethality, and reduced expression of adipogenic genes (Pparg, Cebpa, Krox20, Stat3). Nelfb promotes open chromatin structure and stabilizes RNA Pol II binding at these gene loci. Retroviral expression of Pparg in Nelfb-depleted cells restored adipocyte differentiation; treatment of Nelfb-deleted mice with the PPARγ agonist rosiglitazone allowed dWAT formation and prolonged lifespan.\",\n      \"method\": \"Conditional knockout mouse (preadipocyte-specific), chromatin accessibility assays, Pol II ChIP, retroviral rescue (Pparg), pharmacological rescue (rosiglitazone), cell differentiation assays\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional KO with defined developmental phenotype, ChIP linking NELFB to Pol II occupancy at specific loci, orthogonal genetic and pharmacological rescue experiments\",\n      \"pmids\": [\"40960263\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"The genetic interaction between Brca1 and Cobra1 in mammary gland development is domain- and gene-specific: separation-of-function Brca1 mutations abrogating either its RING domain E3 ligase activity or BRCT domain phospho-recognition do not rescue Cobra1 KO mammary defects, and deletion of Palb2 also does not rescue these defects, unlike full-length Brca1 loss.\",\n      \"method\": \"Conditional double-knockout mice (Brca1 separation-of-function alleles × Cobra1 KO), mammary gland phenotypic analysis\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with separation-of-function alleles, clean in vivo phenotype, single lab\",\n      \"pmids\": [\"29426838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"COBRA1 positively influences androgen receptor (AR) target gene expression and promoter activity in prostate cancer cells; depletion decreases cell viability, proliferation, and anchorage-independent growth, while overexpression of COBRA1 allows AR-positive cells to survive under androgen-deprivation conditions.\",\n      \"method\": \"siRNA knockdown and ectopic overexpression, reporter/promoter activity assays, cell viability/proliferation assays, androgen deprivation experiments\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — functional cell-based assays with KD and OE, promoter activity assays linking COBRA1 to AR target gene regulation, single lab\",\n      \"pmids\": [\"30036938\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Gene expression profiling after shRNA-mediated knockdown of COBRA1 and BRCA1 separately in breast cancer cells reveals a significant overlap in the sets of genes regulated by each factor, supporting shared gene regulatory pathways.\",\n      \"method\": \"shRNA knockdown, gene expression microarray\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — microarray after separate KDs without direct protein interaction or pathway placement experiments; overlap is correlative\",\n      \"pmids\": [\"18071589\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NELFB (COBRA1/NELF-B) is a subunit of the four-component NELF complex that stabilizes promoter-proximal RNA Polymerase II pausing to regulate transcription elongation; it directly interacts with BRCA1 and antagonizes its transcriptional function during mammary gland development, binds AP-1 components (c-Jun/c-Fos) and the glucocorticoid receptor pathway to attenuate their transcriptional output, mediates TrkC dependence-receptor apoptosis by shuttling a proteolytic TrkC killer fragment to the mitochondria to activate Bax and cytochrome c release, and—separately from its nuclear Pol II pausing role—functions in the cytoplasm by interacting with PI3K/AKT to support cell proliferation, with structural studies defining the NELF-B/C/E ternary complex interface.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NELFB (COBRA1/NELF-B) is a subunit of the NELF complex that controls transcription elongation by stabilizing promoter-proximal RNA Polymerase II and shaping gene-specific output during development [#0, #8]. Through this activity it is essential for early embryogenesis and inner cell mass integrity, where it binds developmental promoters such as Lef1 and modulates promoter-bound Pol II to restrain precocious differentiation [#0], and it drives lineage-specific programs in mammary epithelium [#1] and in adipocyte differentiation, where it promotes open chromatin and stabilizes Pol II at adipogenic loci (Pparg, Cebpa) to enable adipose tissue formation [#8]. In the nucleus NELFB functions as a transcriptional antagonist of multiple regulatory pathways: it physically interacts with BRCA1 in a DNA repair-independent manner and antagonizes BRCA1 control of the developmental transcription program [#1, #4], binds the AP-1 components c-Jun and c-Fos to inhibit AP-1 transcriptional activity [#3], and attenuates glucocorticoid receptor-mediated gene induction by reducing GR promoter recruitment [#5]. Structurally, NELFB forms a defined ternary interface with NELF-C and NELF-E [#6]. Beyond transcription, NELFB has separable cytoplasmic functions: it shuttles the proteolytic TrkC killer fragment to mitochondria to trigger Bax activation, cytochrome c release, and apoptosis [#2], and a cytoplasm-restricted pool interacts with PI3K/AKT to support cell proliferation independently of its Pol II pausing role [#7].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing that COBRA1 is a nuclear partner and repressor of transcription factors gave it a defined regulatory role, first by showing it binds BRCA1 and inhibits AP-1.\",\n      \"evidence\": \"Endogenous co-immunoprecipitation and immunofluorescence (BRCA1) plus Co-IP, domain mapping, and reporter assays (c-Jun/c-Fos)\",\n      \"pmids\": [\"15185750\", \"15530430\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether BRCA1 binding is direct versus complex-mediated was not resolved\", \"The mechanism linking AP-1 binding to Pol II elongation control was not established\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Comparing transcriptomes after COBRA1 versus BRCA1 knockdown asked whether the two factors share gene targets, supporting a common regulatory pathway.\",\n      \"evidence\": \"shRNA knockdown with gene expression microarray in breast cancer cells\",\n      \"pmids\": [\"18071589\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Overlap is correlative without direct interaction or epistasis\", \"Does not distinguish shared targets from independent regulation of the same genes\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Knockout in mice and ESCs answered whether COBRA1 has a developmental requirement, showing it maintains the undifferentiated state by tuning Pol II at developmental promoters.\",\n      \"evidence\": \"Knockout mouse, shRNA in ESCs, and ChIP at the Lef1 promoter\",\n      \"pmids\": [\"19340312\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The full set of direct promoter targets was not mapped\", \"How COBRA1 distinguishes genes to pause was not defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Two studies expanded NELFB beyond Pol II pausing: one showed it executes dependence-receptor apoptosis, the other that it decelerates glucocorticoid receptor signaling.\",\n      \"evidence\": \"Co-IP, subcellular fractionation, apoptosis assays, and in vivo chick neural tube silencing (TrkC); shRNA, ChIP, competition assays, and motif mutagenesis (GR)\",\n      \"pmids\": [\"24034695\", \"24097989\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The molecular signal triggering NELFB cytoplasmic-to-mitochondrial shuttling in TrkC apoptosis was not defined\", \"Whether GR attenuation operates through the NELF pausing complex or independently was not separated\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Conditional mammary knockout with Brca1 epistasis established that BRCA1 antagonizes the COBRA1 transcription program independently of DNA repair, defining their developmental relationship.\",\n      \"evidence\": \"Tissue-specific Cobra1 KO, Brca1/Cobra1 double-KO genetic suppression, and transcription analysis\",\n      \"pmids\": [\"26941120\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The biochemical mechanism by which BRCA1 counteracts COBRA1 was not defined\", \"Which specific COBRA1 target genes drive the mammary phenotype was not pinpointed\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Separation-of-function Brca1 alleles refined the antagonism, showing neither BRCA1 enzymatic nor phospho-recognition activity nor PALB2 rescues Cobra1 loss, narrowing the relevant BRCA1 function.\",\n      \"evidence\": \"Conditional double-KO mice with Brca1 RING and BRCT mutant alleles and Palb2 deletion\",\n      \"pmids\": [\"29426838\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The specific BRCA1 domain or activity that opposes COBRA1 remains unidentified\", \"Single-lab in vivo result without biochemical reconstitution\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Prostate cancer studies showed COBRA1 acts as a positive regulator of androgen receptor target genes, indicating its transcriptional effect is context- and factor-dependent rather than uniformly repressive.\",\n      \"evidence\": \"siRNA knockdown, overexpression, promoter reporter and proliferation assays under androgen deprivation\",\n      \"pmids\": [\"30036938\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Whether COBRA1 directly binds AR or its promoters was not shown\", \"The mechanistic basis for positive versus negative transcriptional effects was not resolved\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"A crystal structure and a separation-of-function study together resolved how NELFB assembles into the NELF complex and uncoupled its cytoplasmic proliferative role from nuclear pausing.\",\n      \"evidence\": \"X-ray crystallography of the NELF-B/C/E ternary complex; nuclear-exclusion mutants, Co-IP, Pol II ChIP, and membrane-tethered PI3K/AKT rescue\",\n      \"pmids\": [\"37591184\", \"37717699\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The cytoplasmic NELFB–PI3K/AKT interaction was not structurally defined\", \"How a single protein partitions between nuclear pausing and cytoplasmic signaling functions was not fully explained\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Preadipocyte-specific knockout established a NELFB requirement in adipogenesis, showing it enables open chromatin and Pol II loading at master adipogenic genes, with PPARγ acting downstream.\",\n      \"evidence\": \"Conditional KO mouse, chromatin accessibility and Pol II ChIP, retroviral Pparg rescue, and rosiglitazone pharmacological rescue\",\n      \"pmids\": [\"40960263\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"How NELFB promotes chromatin opening mechanistically was not defined\", \"Whether this depends on the canonical NELF complex was not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unresolved how NELFB selects specific genes for pausing versus activation across tissues, and what governs the partition between its nuclear transcriptional and cytoplasmic apoptotic/proliferative functions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No unifying mechanism explains positive versus negative transcriptional outcomes\", \"The trafficking signals controlling nuclear versus cytoplasmic NELFB are undefined\", \"No direct biochemical link between the structural NELF interface and tissue-specific phenotypes\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [0, 1, 3, 5, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [0, 1, 5, 8]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [0, 1, 8]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"NELF complex\",\n      \"NELF-B/C/E ternary complex\"\n    ],\n    \"partners\": [\n      \"BRCA1\",\n      \"c-Jun\",\n      \"c-Fos\",\n      \"TrkC\",\n      \"NELFE\",\n      \"NELFC\",\n      \"PIK3CA\",\n      \"AKT1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}