{"gene":"DEPP1","run_date":"2026-04-28T17:46:02","timeline":{"discoveries":[{"year":2005,"finding":"DEPP (decidual protein induced by progesterone) was cloned from human endometrial stromal cell cDNA library; it increases phosphorylated ERK levels and activates the Elk-1 transcription factor in HEK293 cells, placing DEPP upstream of ERK/Elk-1 signaling during decidualization.","method":"Overexpression in HEK293 cells, ERK phosphorylation assay, Elk-1 reporter assay","journal":"Molecular human reproduction","confidence":"Medium","confidence_rationale":"Tier 3 — single lab, single overexpression experiment with functional readout but no mutagenesis or binding partner identification","pmids":["16123073"],"is_preprint":false},{"year":2011,"finding":"DEPP expression in human endothelial cells is transcriptionally regulated by FoxO transcription factors via two functional FoxO-responsive elements identified in the DEPP promoter; hypoxia-induced DEPP upregulation is FoxO-dependent.","method":"Reporter assay (DEPP promoter-luciferase), FoxO knockdown/overexpression, hypoxia treatment in EA.hy926 cells","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 — promoter functional mapping plus genetic (siRNA) epistasis in two conditions","pmids":["21510935"],"is_preprint":false},{"year":2014,"finding":"DEPP localizes to peroxisomes and mitochondria in neuroblastoma cells via an N-terminal peroxisomal-targeting-signal-type-2 (PTS2) sequence; it directly binds the PEX7 peroxisomal import receptor (co-immunoprecipitation); DEPP overexpression reduces catalase activity and elevates ROS, while knockdown increases catalase activity and PPARG expression, establishing DEPP as an impairment of peroxisomal ROS detoxification.","method":"Confocal microscopy of EYFP-tagged DEPP with peroxisomal/mitochondrial probes, co-immunoprecipitation with PEX7, catalase activity assay, siRNA knockdown, conditional overexpression","journal":"Molecular cancer","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods (localization, co-IP, enzymatic assay, gain- and loss-of-function) in one study","pmids":["25261981"],"is_preprint":false},{"year":2014,"finding":"DEPP is a major hypoxia-inducible gene regulated by oxidative stress (EC-SOD); overexpressed DEPP co-localizes with protein aggregates/aggresomes and is rapidly degraded by the proteasome; DEPP overexpression activates autophagy, and DEPP silencing attenuates autophagy, linking DEPP to the autophagy pathway.","method":"Subcellular fractionation, immunofluorescence microscopy, proteasome inhibitor treatment, autophagy modulation (3-methyladenine, rapamycin), siRNA knockdown, EC-SOD overexpression mouse model","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 2 — multiple methods in one lab; orthogonal approaches for localization and autophagy phenotype","pmids":["24530860"],"is_preprint":false},{"year":2017,"finding":"DEPP mediates FOXO3-induced autophagy in neuroblastoma by inducing ROS accumulation; DEPP knockdown is sufficient to block autophagy under serum starvation and genotoxic stress, and N-acetyl-cysteine (ROS scavenger) fully blocks DEPP-induced autophagosome formation, positioning ROS accumulation as the mechanistic link between DEPP and autophagy.","method":"Live-cell fluorescence microscopy (EYFP-LC3), immunoblot (LC3), ROS measurement (MitoTracker Red), siRNA knockdown of DEPP and LC3, N-acetyl-cysteine treatment, flow cytometry","journal":"Molecular cancer","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods, epistasis established by chemical rescue, replicated across stress conditions","pmids":["28545464"],"is_preprint":false},{"year":2018,"finding":"Ectopic DEPP expression in HCT116 colon cancer cells activates Ras/Raf/MEK/ERK and p16INK4A/Rb signaling pathways and induces cellular senescence (SA-β-Gal activity); DEPP knockdown counteracts drug-induced senescence, growth inhibition, and cell cycle arrest, establishing DEPP as a positive regulator of RAS/ERK-driven senescence.","method":"Ectopic overexpression, siRNA knockdown, SA-β-Gal assay, Western blot for pathway components, xenograft mouse model","journal":"Cell death & disease","confidence":"Medium","confidence_rationale":"Tier 2 — gain- and loss-of-function with pathway readout and in vivo validation, single lab","pmids":["29440765"],"is_preprint":false},{"year":2018,"finding":"Hepatic overexpression of DEPP in mice promotes fatty acid oxidation and ketogenesis and suppresses lipogenesis and gluconeogenesis; DEPP increases hepatic ROS by impairing the ROS scavenging system; FGF21, upregulated in response to DEPP-induced oxidative stress, mediates the effects of DEPP on fatty acid oxidation, ketogenesis and lipid synthesis (but not gluconeogenesis), as shown by FGF21 antibody blockade.","method":"Adenovirus-mediated hepatic overexpression in mice, indirect calorimetry, biochemical assays (liver TG, glycogen, β-hydroxybutyrate), catalase activity assay, live-cell ROS fluorescence, qPCR, FGF21 antibody neutralization, db/db mouse model","journal":"FASEB journal","confidence":"High","confidence_rationale":"Tier 1–2 — in vivo overexpression with mechanistic dissection via antibody epistasis and multiple metabolic readouts","pmids":["29702025"],"is_preprint":false},{"year":2009,"finding":"DEPP mRNA is highly expressed in white adipose tissue and is regulated by insulin: insulin treatment significantly decreases DEPP mRNA in 3T3-L1 adipocytes, rat H4IIE, and human HepG2 hepatoma cells; fasting induces and refeeding suppresses hepatic/adipose DEPP expression in vivo, identifying insulin as a negative regulator of DEPP.","method":"Northern blot, in vitro insulin treatment of multiple cell lines, in vivo fasting/refeeding experiments, streptozotocin-induced diabetic mouse model","journal":"Hormone and metabolic research","confidence":"Medium","confidence_rationale":"Tier 2 — replicated across multiple cell lines and in vivo models in one study","pmids":["19937567"],"is_preprint":false},{"year":2018,"finding":"DEPP overexpression in HCT116 colon cancer cells promotes MAPK (ERK, JNK, p38) phosphorylation and upregulates Gadd45a; DEPP or Gadd45a knockdown impairs baicalein-induced apoptosis, caspase-3/9 activation, and MAPK phosphorylation; JNK/p38 inhibition decreases Gadd45a expression, establishing a DEPP→MAPK→Gadd45a positive feedback loop leading to apoptosis.","method":"siRNA knockdown of DEPP and Gadd45a, Annexin V/PI apoptosis assay, caspase activity assay, Western blot for phospho-MAPKs, kinase inhibitors (SP600125, SB203580, SCH772984)","journal":"International journal of oncology","confidence":"Medium","confidence_rationale":"Tier 2 — epistasis established with multiple inhibitors and siRNA, single lab","pmids":["29749481"],"is_preprint":false},{"year":2022,"finding":"DEPP activates mitochondrial autophagy (mitophagy) in chondrocytes via BCL2 interacting protein 3 (BNIP3); DEPP is downstream of FOXO transcription factors in chondrocytes; DEPP knockout mice show exacerbated cartilage degradation with decreased autophagic flux and increased chondrocyte death, establishing DEPP as a stress-inducible regulator of mitophagy in osteoarthritis.","method":"DEPP knockdown/overexpression in chondrocytes, autophagic flux measurement, FOXO knockdown, subcellular fractionation, DEPP-knockout mice (destabilization of medial meniscus OA model), TUNEL assay","journal":"FASEB journal","confidence":"High","confidence_rationale":"Tier 2 — in vivo knockout model combined with cell-based mechanistic studies and identification of BNIP3 as downstream effector","pmids":["34997944"],"is_preprint":false},{"year":2024,"finding":"DEPP1 is induced by HIF (hypoxia-inducible factor) under hypoxia in cardiomyocytes; DEPP1 localizes inside mitochondria; DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes; whole-body Depp1 knockout decreases cardiac dysfunction in mice with chronic HIF activation (VHL cardiac knockout), establishing DEPP1 as a key HIF-downstream mediator of ischemic cardiomyopathy features.","method":"CRISPR-Cas9 Depp1 knockout mice, cardiac pVHL-knockout mice, RNA sequencing, immunoblot, mitochondrial and peroxisomal autophagy flux measurements, live-cell imaging of isolated cardiomyocytes","journal":"Circulation","confidence":"High","confidence_rationale":"Tier 1–2 — in vivo CRISPR knockout with gain-of-function epistasis, multiple orthogonal methods including organelle-specific autophagy flux and cardiac phenotype","pmids":["38881449"],"is_preprint":false}],"current_model":"DEPP1 (C10ORF10/DEPP) is a HIF- and FOXO3-transcriptional target that localizes to peroxisomes (via PTS2/PEX7) and mitochondria, where it impairs ROS detoxification by reducing catalase activity, thereby elevating cellular ROS that drive autophagy (including mitophagy via BNIP3), activate ERK/MAPK and senescence pathways, and induce FGF21-mediated metabolic reprogramming; in cardiac tissue, DEPP1 is necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation, making it a central mediator linking hypoxia/FOXO signaling to organelle quality control and metabolic disease."},"narrative":{"teleology":[{"year":2005,"claim":"Initial cloning established that DEPP1 is not merely a decidualization marker but an active signaling molecule capable of engaging the ERK/Elk-1 pathway, raising the question of its upstream inputs and downstream consequences.","evidence":"Overexpression in HEK293 cells with ERK phosphorylation and Elk-1 reporter assays","pmids":["16123073"],"confidence":"Medium","gaps":["No endogenous loss-of-function data","Mechanism of ERK activation unknown","No binding partner or direct substrate identified"]},{"year":2009,"claim":"Identification of insulin as a negative regulator and fasting as a positive regulator of DEPP1 expression placed the gene within nutrient-sensing circuitry, though the downstream metabolic consequences remained undefined.","evidence":"Northern blot across tissues and cell lines, fasting/refeeding and streptozotocin diabetic mouse models","pmids":["19937567"],"confidence":"Medium","gaps":["No mechanism linking insulin signaling to DEPP1 promoter","Functional consequence of DEPP1 induction during fasting not tested"]},{"year":2011,"claim":"Mapping of two functional FoxO-responsive elements in the DEPP1 promoter resolved how hypoxia and stress transcriptionally upregulate the gene, establishing DEPP1 as a direct FOXO transcriptional target.","evidence":"Promoter-luciferase reporters with site mutagenesis, FoxO knockdown/overexpression under normoxia and hypoxia in EA.hy926 endothelial cells","pmids":["21510935"],"confidence":"Medium","gaps":["HIF-responsive elements not yet mapped","No chromatin immunoprecipitation to confirm direct FoxO occupancy"]},{"year":2014,"claim":"Determining that DEPP1 localizes to peroxisomes via PTS2/PEX7 and to mitochondria, and that it impairs catalase activity to elevate ROS, provided the first mechanistic explanation for its cellular function and linked it to organelle-level redox control.","evidence":"Confocal microscopy of EYFP-tagged DEPP1, co-immunoprecipitation with PEX7, catalase activity assays, gain- and loss-of-function in neuroblastoma cells","pmids":["25261981"],"confidence":"High","gaps":["Molecular mechanism by which DEPP1 inhibits catalase (direct binding vs. indirect) unclear","Relative functional importance of peroxisomal vs. mitochondrial pools not resolved"]},{"year":2014,"claim":"Demonstration that DEPP1 overexpression activates autophagy and that silencing attenuates it established autophagy induction as a major downstream output, though the signaling intermediary (ROS) was not yet proven.","evidence":"Autophagy modulation with 3-methyladenine and rapamycin, siRNA knockdown, EC-SOD overexpression mouse model, proteasome inhibitor treatment","pmids":["24530860"],"confidence":"Medium","gaps":["Causal role of ROS in DEPP1-driven autophagy not directly tested","Selectivity of autophagy (mitophagy vs. bulk) uncharacterized"]},{"year":2017,"claim":"Chemical rescue with N-acetyl-cysteine proved that ROS accumulation is the obligate intermediary between DEPP1 and autophagosome formation, closing the mechanistic gap between peroxisomal catalase inhibition and autophagy activation.","evidence":"Live-cell LC3 imaging, ROS measurement, NAC rescue, siRNA epistasis across starvation and genotoxic stress in neuroblastoma cells","pmids":["28545464"],"confidence":"High","gaps":["Identity of the ROS sensor linking peroxisomal ROS to autophagy machinery unknown","Whether mitophagy specifically requires DEPP1-ROS axis not tested"]},{"year":2018,"claim":"Three studies collectively expanded the functional repertoire of DEPP1 beyond autophagy: hepatic DEPP1 drives FGF21-dependent fatty acid oxidation and ketogenesis; DEPP1 activates Ras/ERK to induce senescence; and a DEPP1→MAPK→Gadd45a feedback loop promotes apoptosis—all converging on ROS as the common upstream signal.","evidence":"Adenovirus-mediated hepatic overexpression with FGF21 antibody neutralization in mice; ectopic expression and siRNA in HCT116 with SA-β-Gal, MAPK blots, and kinase inhibitor epistasis; xenograft models","pmids":["29702025","29440765","29749481"],"confidence":"Medium","gaps":["FGF21 mediates fatty acid oxidation but not gluconeogenesis effects—alternate pathway unidentified","Direct physical interaction between DEPP1 and Ras/Raf components not established","Relative contributions of ERK vs. JNK/p38 to different DEPP1 phenotypes unclear"]},{"year":2022,"claim":"DEPP1 knockout mice with surgically induced osteoarthritis showed exacerbated cartilage degradation, establishing DEPP1 as a physiologically relevant stress-protective factor and identifying BNIP3 as the downstream effector coupling DEPP1 to mitophagy in chondrocytes.","evidence":"DEPP1-knockout mice with destabilized medial meniscus model, autophagic flux measurement, BNIP3 epistasis, TUNEL assay","pmids":["34997944"],"confidence":"High","gaps":["Whether BNIP3 upregulation is a direct ROS effect or requires transcriptional intermediaries unknown","Peroxisomal autophagy contribution in chondrocytes not assessed"]},{"year":2024,"claim":"CRISPR knockout of Depp1 in mice demonstrated that DEPP1 is necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation in cardiomyocytes, and that its loss ameliorates cardiac dysfunction under chronic HIF activation, positioning DEPP1 as a central mediator of ischemic cardiomyopathy pathology.","evidence":"Whole-body CRISPR-Cas9 Depp1 knockout crossed with cardiac VHL-knockout mice, organelle-specific autophagy flux, RNA-seq, live-cell imaging of cardiomyocytes","pmids":["38881449"],"confidence":"High","gaps":["Mitochondrial import mechanism of DEPP1 not resolved","Molecular basis of triglyceride accumulation downstream of DEPP1 not defined","Whether cardiac phenotype rescue is cell-autonomous to cardiomyocytes not formally demonstrated with conditional knockout"]},{"year":null,"claim":"The direct molecular mechanism by which DEPP1 inhibits catalase—whether through physical binding, post-translational modification, or displacement from peroxisomes—remains unresolved, as does the identity of the ROS sensor that couples DEPP1-elevated ROS to autophagy initiation machinery.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural or biochemical reconstitution of DEPP1-catalase interaction","ROS sensor or adaptor linking peroxisomal ROS to autophagosome nucleation unknown","Tissue-specific differences in DEPP1 function (cardiac vs. hepatic vs. chondrocyte) not mechanistically explained"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,4,6]}],"localization":[{"term_id":"GO:0005777","term_label":"peroxisome","supporting_discovery_ids":[2,10]},{"term_id":"GO:0005739","term_label":"mitochondrion","supporting_discovery_ids":[2,10]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[3,4,9,10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[0,5,8]},{"term_id":"R-HSA-8953897","term_label":"Cellular responses to stimuli","supporting_discovery_ids":[1,2,4,6]},{"term_id":"R-HSA-1430728","term_label":"Metabolism","supporting_discovery_ids":[6,7]}],"complexes":[],"partners":["PEX7","BNIP3","FGF21","GADD45A"],"other_free_text":[]},"mechanistic_narrative":"DEPP1 is a stress-inducible peroxisomal and mitochondrial protein that links hypoxia and FOXO3 signaling to organelle-selective autophagy and metabolic reprogramming by elevating cellular reactive oxygen species. It is transcriptionally induced by HIF and FOXO3 (and suppressed by insulin), localizes to peroxisomes via an N-terminal PTS2 signal recognized by the import receptor PEX7, and impairs catalase-dependent ROS detoxification; the resulting ROS accumulation drives autophagosome formation—including BNIP3-dependent mitophagy—as demonstrated by chemical rescue with N-acetyl-cysteine [PMID:25261981, PMID:28545464, PMID:34997944]. DEPP1-induced ROS also activate the Ras/Raf/MEK/ERK cascade, promoting cellular senescence and, in the liver, FGF21-dependent fatty acid oxidation and ketogenesis [PMID:29440765, PMID:29702025, PMID:29749481]. In cardiomyocytes, DEPP1 is both necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation, and whole-body Depp1 knockout ameliorates cardiac dysfunction in a mouse model of chronic HIF activation [PMID:38881449]."},"prefetch_data":{"uniprot":{"accession":"Q9NTK1","full_name":"Protein DEPP1","aliases":["Decidual protein induced by progesterone","Fasting-induced gene protein","FIG"],"length_aa":212,"mass_kda":23.4,"function":"Acts as a critical modulator of FOXO3-induced autophagy via increased cellular ROS","subcellular_location":"Cytoplasm; Peroxisome; Mitochondrion","url":"https://www.uniprot.org/uniprotkb/Q9NTK1/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DEPP1","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/DEPP1","total_profiled":1310},"omim":[{"mim_id":"611309","title":"DEPP1 AUTOPHAGY REGULATOR; DEPP1","url":"https://www.omim.org/entry/611309"},{"mim_id":"601162","title":"SPASTIC PARAPLEGIA 9A, AUTOSOMAL DOMINANT; SPG9A","url":"https://www.omim.org/entry/601162"},{"mim_id":"219150","title":"CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IIIA; ARCL3A","url":"https://www.omim.org/entry/219150"},{"mim_id":"138250","title":"ALDEHYDE DEHYDROGENASE 18 FAMILY, MEMBER A1; ALDH18A1","url":"https://www.omim.org/entry/138250"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Mitochondria","reliability":"Supported"},{"location":"Vesicles","reliability":"Additional"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"adipose tissue","ntpm":858.3},{"tissue":"breast","ntpm":687.9}],"url":"https://www.proteinatlas.org/search/DEPP1"},"hgnc":{"alias_symbol":["DEPP","FIG","Fseg"],"prev_symbol":["C10orf10"]},"alphafold":{"accession":"Q9NTK1","domains":[],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NTK1","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NTK1-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NTK1-F1-predicted_aligned_error_v6.png","plddt_mean":59.78},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DEPP1","jax_strain_url":"https://www.jax.org/strain/search?query=DEPP1"},"sequence":{"accession":"Q9NTK1","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NTK1.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NTK1/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NTK1"}},"corpus_meta":[{"pmid":"22848088","id":"PMC_22848088","title":"An extreme case of plant-insect codiversification: figs and fig-pollinating wasps.","date":"2012","source":"Systematic biology","url":"https://pubmed.ncbi.nlm.nih.gov/22848088","citation_count":182,"is_preprint":false},{"pmid":"12661006","id":"PMC_12661006","title":"Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21).","date":"2003","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/12661006","citation_count":171,"is_preprint":false},{"pmid":"29209349","id":"PMC_29209349","title":"Regulation of Fig (Ficus carica L.) Fruit Color: Metabolomic and Transcriptomic Analyses of the Flavonoid Biosynthetic Pathway.","date":"2017","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/29209349","citation_count":139,"is_preprint":false},{"pmid":"29440765","id":"PMC_29440765","title":"Baicalin induces cellular senescence in human colon cancer cells via upregulation of DEPP and the activation of Ras/Raf/MEK/ERK signaling.","date":"2018","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/29440765","citation_count":96,"is_preprint":false},{"pmid":"33035453","id":"PMC_33035453","title":"Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution.","date":"2020","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/33035453","citation_count":94,"is_preprint":false},{"pmid":"11473446","id":"PMC_11473446","title":"Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation.","date":"2001","source":"Journal of natural products","url":"https://pubmed.ncbi.nlm.nih.gov/11473446","citation_count":88,"is_preprint":false},{"pmid":"24359812","id":"PMC_24359812","title":"Obligate mutualism within a host drives the extreme specialization of a fig wasp genome.","date":"2013","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/24359812","citation_count":85,"is_preprint":false},{"pmid":"28545464","id":"PMC_28545464","title":"C10ORF10/DEPP-mediated ROS accumulation is a critical modulator of FOXO3-induced autophagy.","date":"2017","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/28545464","citation_count":82,"is_preprint":false},{"pmid":"11603937","id":"PMC_11603937","title":"Molecular phylogenies of fig wasps: partial cocladogenesis of pollinators and parasites.","date":"2001","source":"Molecular phylogenetics and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/11603937","citation_count":72,"is_preprint":false},{"pmid":"24154728","id":"PMC_24154728","title":"Mouse model of intrahepatic cholangiocarcinoma validates FIG-ROS as a potent fusion oncogene and therapeutic target.","date":"2013","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/24154728","citation_count":65,"is_preprint":false},{"pmid":"19777155","id":"PMC_19777155","title":"Complete nucleotide sequence of four RNA segments of fig mosaic virus.","date":"2009","source":"Archives of virology","url":"https://pubmed.ncbi.nlm.nih.gov/19777155","citation_count":58,"is_preprint":false},{"pmid":"14965908","id":"PMC_14965908","title":"Correlated evolution in fig pollination.","date":"2004","source":"Systematic biology","url":"https://pubmed.ncbi.nlm.nih.gov/14965908","citation_count":51,"is_preprint":false},{"pmid":"29749481","id":"PMC_29749481","title":"Baicalein induces the apoptosis of HCT116 human colon cancer cells via the upregulation of DEPP/Gadd45a and activation of MAPKs.","date":"2018","source":"International journal of oncology","url":"https://pubmed.ncbi.nlm.nih.gov/29749481","citation_count":50,"is_preprint":false},{"pmid":"25261981","id":"PMC_25261981","title":"C10ORF10/DEPP, a transcriptional target of FOXO3, regulates ROS-sensitivity in human neuroblastoma.","date":"2014","source":"Molecular cancer","url":"https://pubmed.ncbi.nlm.nih.gov/25261981","citation_count":48,"is_preprint":false},{"pmid":"37208612","id":"PMC_37208612","title":"DePolymerase Predictor (DePP): a machine learning tool for the targeted identification of phage depolymerases.","date":"2023","source":"BMC bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/37208612","citation_count":47,"is_preprint":false},{"pmid":"17444902","id":"PMC_17444902","title":"Host-specificity and coevolution among pollinating and nonpollinating New World fig wasps.","date":"2007","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/17444902","citation_count":46,"is_preprint":false},{"pmid":"7756696","id":"PMC_7756696","title":"Novel Ti plasmids in Agrobacterium strains isolated from fig tree and chrysanthemum tumors and their opinelike molecules.","date":"1995","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/7756696","citation_count":46,"is_preprint":false},{"pmid":"22671555","id":"PMC_22671555","title":"Wolbachia infection and dramatic intraspecific mitochondrial DNA divergence in a fig wasp.","date":"2012","source":"Evolution; international journal of organic evolution","url":"https://pubmed.ncbi.nlm.nih.gov/22671555","citation_count":45,"is_preprint":false},{"pmid":"22992110","id":"PMC_22992110","title":"An integrated badnavirus is prevalent in fig germplasm.","date":"2012","source":"Phytopathology","url":"https://pubmed.ncbi.nlm.nih.gov/22992110","citation_count":44,"is_preprint":false},{"pmid":"12116930","id":"PMC_12116930","title":"Phylogenetic relationships of fig wasps pollinating functionally dioecious Ficus based on mitochondrial DNA sequences and morphology.","date":"2001","source":"Systematic biology","url":"https://pubmed.ncbi.nlm.nih.gov/12116930","citation_count":39,"is_preprint":false},{"pmid":"31808196","id":"PMC_31808196","title":"Epigenetic patterns within the haplotype phased fig (Ficus carica L.) genome.","date":"2020","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/31808196","citation_count":38,"is_preprint":false},{"pmid":"27075252","id":"PMC_27075252","title":"Pollinator sharing and gene flow among closely related sympatric dioecious fig taxa.","date":"2016","source":"Proceedings. Biological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/27075252","citation_count":35,"is_preprint":false},{"pmid":"34691109","id":"PMC_34691109","title":"Genome-Wide Characterization and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Fig (Ficus carica L.).","date":"2021","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/34691109","citation_count":35,"is_preprint":false},{"pmid":"24530860","id":"PMC_24530860","title":"The c10orf10 gene product is a new link between oxidative stress and autophagy.","date":"2014","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/24530860","citation_count":34,"is_preprint":false},{"pmid":"32109281","id":"PMC_32109281","title":"Genetic Diversity and Thermal Performance in Invasive and Native Populations of African Fig Flies.","date":"2020","source":"Molecular biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/32109281","citation_count":34,"is_preprint":false},{"pmid":"18078703","id":"PMC_18078703","title":"Cytotoxicity of fig fruit latex against human cancer cells.","date":"2007","source":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","url":"https://pubmed.ncbi.nlm.nih.gov/18078703","citation_count":32,"is_preprint":false},{"pmid":"16123073","id":"PMC_16123073","title":"A novel protein Depp, which is induced by progesterone in human endometrial stromal cells activates Elk-1 transcription factor.","date":"2005","source":"Molecular human reproduction","url":"https://pubmed.ncbi.nlm.nih.gov/16123073","citation_count":31,"is_preprint":false},{"pmid":"18386067","id":"PMC_18386067","title":"Correlated evolution of fig size and color supports the dispersal syndromes hypothesis.","date":"2008","source":"Oecologia","url":"https://pubmed.ncbi.nlm.nih.gov/18386067","citation_count":31,"is_preprint":false},{"pmid":"31732029","id":"PMC_31732029","title":"Nutritional, chemical and bioactive profiles of different parts of a Portuguese common fig (Ficus carica L.) variety.","date":"2019","source":"Food research international (Ottawa, Ont.)","url":"https://pubmed.ncbi.nlm.nih.gov/31732029","citation_count":28,"is_preprint":false},{"pmid":"33421307","id":"PMC_33421307","title":"Fig fruit ripening is regulated by the interaction between ethylene and abscisic acid.","date":"2021","source":"Journal of integrative plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/33421307","citation_count":27,"is_preprint":false},{"pmid":"26648752","id":"PMC_26648752","title":"Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma.","date":"2015","source":"Cancer growth and metastasis","url":"https://pubmed.ncbi.nlm.nih.gov/26648752","citation_count":27,"is_preprint":false},{"pmid":"35485976","id":"PMC_35485976","title":"DEPP: Deep Learning Enables Extending Species Trees using Single Genes.","date":"2023","source":"Systematic biology","url":"https://pubmed.ncbi.nlm.nih.gov/35485976","citation_count":26,"is_preprint":false},{"pmid":"23609162","id":"PMC_23609162","title":"Diel variation in fig volatiles across syconium development: making sense of scents.","date":"2013","source":"Journal of chemical ecology","url":"https://pubmed.ncbi.nlm.nih.gov/23609162","citation_count":26,"is_preprint":false},{"pmid":"30764262","id":"PMC_30764262","title":"Partial Sequence and Survey Analysis Identify a Multipartite, Negative-Sense RNA Virus Associated with Fig Mosaic.","date":"2009","source":"Plant disease","url":"https://pubmed.ncbi.nlm.nih.gov/30764262","citation_count":26,"is_preprint":false},{"pmid":"23342036","id":"PMC_23342036","title":"Evolution and expression plasticity of opsin genes in a fig pollinator, Ceratosolen solmsi.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23342036","citation_count":24,"is_preprint":false},{"pmid":"25231053","id":"PMC_25231053","title":"Screening for the FIG-ROS1 fusion in biliary tract carcinomas by nested PCR.","date":"2014","source":"Genes, chromosomes & cancer","url":"https://pubmed.ncbi.nlm.nih.gov/25231053","citation_count":23,"is_preprint":false},{"pmid":"25320328","id":"PMC_25320328","title":"Nucleocapsid protein from fig mosaic virus forms cytoplasmic agglomerates that are hauled by endoplasmic reticulum streaming.","date":"2014","source":"Journal of virology","url":"https://pubmed.ncbi.nlm.nih.gov/25320328","citation_count":23,"is_preprint":false},{"pmid":"34997944","id":"PMC_34997944","title":"C10orf10/DEPP activates mitochondrial autophagy and maintains chondrocyte viability in the pathogenesis of osteoarthritis.","date":"2022","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/34997944","citation_count":22,"is_preprint":false},{"pmid":"21510935","id":"PMC_21510935","title":"FoxO regulates expression of decidual protein induced by progesterone (DEPP) in human endothelial cells.","date":"2011","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/21510935","citation_count":22,"is_preprint":false},{"pmid":"30719217","id":"PMC_30719217","title":"ROS1-GOPC/FIG: a novel gene fusion in hepatic angiosarcoma.","date":"2019","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/30719217","citation_count":21,"is_preprint":false},{"pmid":"30656555","id":"PMC_30656555","title":"Cytokinin-induced parthenocarpy of San Pedro type fig (Ficus carica L.) main crop: explained by phytohormone assay and transcriptomic network comparison.","date":"2019","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/30656555","citation_count":21,"is_preprint":false},{"pmid":"34433422","id":"PMC_34433422","title":"Metabolome and transcriptome analysis of flavor components and flavonoid biosynthesis in fig female flower tissues (Ficus carica L.) after bagging.","date":"2021","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/34433422","citation_count":20,"is_preprint":false},{"pmid":"31379744","id":"PMC_31379744","title":"A Possible Mechanism: Genistein Improves Metabolism and Induces White Fat Browning Through Modulating Hypothalamic Expression of Ucn3, Depp, and Stc1.","date":"2019","source":"Frontiers in endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/31379744","citation_count":20,"is_preprint":false},{"pmid":"21124735","id":"PMC_21124735","title":"Molecular approaches to identify cryptic species and polymorphic species within a complex community of fig wasps.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21124735","citation_count":19,"is_preprint":false},{"pmid":"35236292","id":"PMC_35236292","title":"Genome-wide analysis of JAZ family genes expression patterns during fig (Ficus carica L.) fruit development and in response to hormone treatment.","date":"2022","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/35236292","citation_count":18,"is_preprint":false},{"pmid":"32771161","id":"PMC_32771161","title":"Characterization of terpene synthase genes potentially involved in black fig fly (Silba adipata) interactions with Ficus carica.","date":"2020","source":"Plant science : an international journal of experimental plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/32771161","citation_count":18,"is_preprint":false},{"pmid":"25039747","id":"PMC_25039747","title":"Odorant-binding protein (OBP) genes affect host specificity in a fig-pollinator mutualistic system.","date":"2014","source":"Insect molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/25039747","citation_count":18,"is_preprint":false},{"pmid":"19937567","id":"PMC_19937567","title":"Insulin-mediated regulation of decidual protein induced by progesterone (DEPP) in adipose tissue and liver.","date":"2009","source":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme","url":"https://pubmed.ncbi.nlm.nih.gov/19937567","citation_count":17,"is_preprint":false},{"pmid":"33185823","id":"PMC_33185823","title":"Ethephon induces coordinated ripening acceleration and divergent coloration responses in fig (Ficus carica L.) flowers and receptacles.","date":"2020","source":"Plant molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/33185823","citation_count":17,"is_preprint":false},{"pmid":"10898664","id":"PMC_10898664","title":"Cloning and expression of an acidic pectin methylesterase from jelly fig (Ficus awkeotsang).","date":"2000","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10898664","citation_count":17,"is_preprint":false},{"pmid":"31122203","id":"PMC_31122203","title":"Differential color development and response to light deprivation of fig (Ficus carica L.) syconia peel and female flower tissues: transcriptome elucidation.","date":"2019","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/31122203","citation_count":17,"is_preprint":false},{"pmid":"28387643","id":"PMC_28387643","title":"Novel GOPC(FIG)-ROS1 fusion in a pediatric high-grade glioma survivor.","date":"2017","source":"Journal of neurosurgery. Pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/28387643","citation_count":17,"is_preprint":false},{"pmid":"23879300","id":"PMC_23879300","title":"Contrasting genetic responses to population fragmentation in a coevolving fig and fig wasp across a mainland-island archipelago.","date":"2013","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/23879300","citation_count":16,"is_preprint":false},{"pmid":"29702025","id":"PMC_29702025","title":"DEPP/DEPP1/C10ORF10 regulates hepatic glucose and fat metabolism partly via ROS-induced FGF21.","date":"2018","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/29702025","citation_count":16,"is_preprint":false},{"pmid":"30991947","id":"PMC_30991947","title":"Proteome and transcriptome analyses reveal key molecular differences between quality parameters of commercial-ripe and tree-ripe fig (Ficus carica L.).","date":"2019","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/30991947","citation_count":16,"is_preprint":false},{"pmid":"36528674","id":"PMC_36528674","title":"Fig latex inhibits the growth of pathogenic bacteria invading human diabetic wounds and accelerates wound closure in diabetic mice.","date":"2022","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36528674","citation_count":16,"is_preprint":false},{"pmid":"30239815","id":"PMC_30239815","title":"The distinct ripening processes in the reproductive and non-reproductive parts of the fig syconium are driven by ABA.","date":"2019","source":"Journal of experimental botany","url":"https://pubmed.ncbi.nlm.nih.gov/30239815","citation_count":16,"is_preprint":false},{"pmid":"21318240","id":"PMC_21318240","title":"The complete nucleotide sequence and genome organization of Fig cryptic virus, a novel bipartite dsRNA virus infecting fig, widely distributed in the Mediterranean basin.","date":"2011","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/21318240","citation_count":16,"is_preprint":false},{"pmid":"17183491","id":"PMC_17183491","title":"Microsporogenesis in Brachiaria dictyoneura (Fig. & De Not.) Stapf (Poaceae: Paniceae).","date":"2006","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/17183491","citation_count":15,"is_preprint":false},{"pmid":"33252120","id":"PMC_33252120","title":"The Effects of Silver Nanoparticles Biosynthesized Using Fig and Olive Extracts on Cutaneous leishmaniasis Induced Inflammation in Female Balb/c Mice.","date":"2020","source":"Bioscience reports","url":"https://pubmed.ncbi.nlm.nih.gov/33252120","citation_count":15,"is_preprint":false},{"pmid":"26090817","id":"PMC_26090817","title":"Metatranscriptome Analysis of Fig Flowers Provides Insights into Potential Mechanisms for Mutualism Stability and Gall Induction.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26090817","citation_count":15,"is_preprint":false},{"pmid":"34524603","id":"PMC_34524603","title":"Genome characterization of fig umbra-like virus.","date":"2021","source":"Virus genes","url":"https://pubmed.ncbi.nlm.nih.gov/34524603","citation_count":14,"is_preprint":false},{"pmid":"33045302","id":"PMC_33045302","title":"Carboxylated nanodiamond-mediated NH2-PLGA nanoparticle-encapsulated fig polysaccharides for strongly enhanced immune responses in vitro and in vivo.","date":"2020","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/33045302","citation_count":14,"is_preprint":false},{"pmid":"27965676","id":"PMC_27965676","title":"Tissue-Specific Transcriptome and Hormonal Regulation of Pollinated and Parthenocarpic Fig (Ficus carica L.) Fruit Suggest that Fruit Ripening Is Coordinated by the Reproductive Part of the Syconium.","date":"2016","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/27965676","citation_count":14,"is_preprint":false},{"pmid":"34650529","id":"PMC_34650529","title":"Novel Symbiotic Association Between Euwallacea Ambrosia Beetle and Fusarium Fungus on Fig Trees in Japan.","date":"2021","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34650529","citation_count":14,"is_preprint":false},{"pmid":"34579394","id":"PMC_34579394","title":"Moderate Salinity Stress Affects Expression of Main Sugar Metabolism and Transport Genes and Soluble Carbohydrate Content in Ripe Fig Fruits (Ficus carica L. cv. Dottato).","date":"2021","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/34579394","citation_count":14,"is_preprint":false},{"pmid":"24849458","id":"PMC_24849458","title":"Competitive exclusion among fig wasps achieved via entrainment of host plant flowering phenology.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24849458","citation_count":14,"is_preprint":false},{"pmid":"20352549","id":"PMC_20352549","title":"Identification, mycotoxin risk and pathogenicity of Fusarium species associated with fig endosepsis in Apulia, Italy.","date":"2010","source":"Food additives & contaminants. Part A, Chemistry, analysis, control, exposure & risk assessment","url":"https://pubmed.ncbi.nlm.nih.gov/20352549","citation_count":14,"is_preprint":false},{"pmid":"29859043","id":"PMC_29859043","title":"Transcriptome analysis unravels spatiotemporal modulation of phytohormone-pathway expression underlying gibberellin-induced parthenocarpic fruit set in San Pedro-type fig (Ficus carica L.).","date":"2018","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/29859043","citation_count":13,"is_preprint":false},{"pmid":"33673593","id":"PMC_33673593","title":"DNA Modification Patterns within the Transposable Elements of the Fig (Ficus carica L.) Genome.","date":"2021","source":"Plants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/33673593","citation_count":13,"is_preprint":false},{"pmid":"30318190","id":"PMC_30318190","title":"Comparison and Assessment of Flixweed and Fig Effects on Irritable Bowel Syndrome with Predominant Constipation: A Single-Blind Randomized Clinical Trial.","date":"2018","source":"Explore (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/30318190","citation_count":12,"is_preprint":false},{"pmid":"37569122","id":"PMC_37569122","title":"Comparative Analysis of the Immune Response and the Clinical Allergic Reaction to Papain-like Cysteine Proteases from Fig, Kiwifruit, Papaya, Pineapple and Mites in an Italian Population.","date":"2023","source":"Foods (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/37569122","citation_count":12,"is_preprint":false},{"pmid":"37316788","id":"PMC_37316788","title":"Polygalacturonase gene family analysis identifies FcPG12 as a key player in fig (Ficus carica L.) fruit softening.","date":"2023","source":"BMC plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/37316788","citation_count":12,"is_preprint":false},{"pmid":"38176487","id":"PMC_38176487","title":"Preparation and characterization of a jelly fig (Ficus awkeotsang Makino) polysaccharide-based bioactive 3D scaffold for improved vascularization and skin tissue engineering applications.","date":"2024","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/38176487","citation_count":12,"is_preprint":false},{"pmid":"34011484","id":"PMC_34011484","title":"Genomes of 12 fig wasps provide insights into the adaptation of pollinators to fig syconia.","date":"2021","source":"Journal of genetics and genomics = Yi chuan xue bao","url":"https://pubmed.ncbi.nlm.nih.gov/34011484","citation_count":12,"is_preprint":false},{"pmid":"33036463","id":"PMC_33036463","title":"Tracking the Distribution and Burst of Nuclear Mitochondrial DNA Sequences (NUMTs) in Fig Wasp Genomes.","date":"2020","source":"Insects","url":"https://pubmed.ncbi.nlm.nih.gov/33036463","citation_count":11,"is_preprint":false},{"pmid":"31494940","id":"PMC_31494940","title":"The nature of interspecific interactions and co-diversification patterns, as illustrated by the fig microcosm.","date":"2019","source":"The New phytologist","url":"https://pubmed.ncbi.nlm.nih.gov/31494940","citation_count":11,"is_preprint":false},{"pmid":"29721823","id":"PMC_29721823","title":"Isolation and Evaluation of New Antagonist Bacillus Strains for the Control of Pathogenic and Mycotoxigenic Fungi of Fig Orchards.","date":"2018","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/29721823","citation_count":11,"is_preprint":false},{"pmid":"33295015","id":"PMC_33295015","title":"Effects of waste fig seed powder on quality as an innovative ingredient in biscuit formulation.","date":"2020","source":"Journal of food science","url":"https://pubmed.ncbi.nlm.nih.gov/33295015","citation_count":11,"is_preprint":false},{"pmid":"38881449","id":"PMC_38881449","title":"Induction of DEPP1 by HIF Mediates Multiple Hallmarks of Ischemic Cardiomyopathy.","date":"2024","source":"Circulation","url":"https://pubmed.ncbi.nlm.nih.gov/38881449","citation_count":10,"is_preprint":false},{"pmid":"37416794","id":"PMC_37416794","title":"AGEs Blocker™ (Goji Berry, Fig, and Korean Mint Mixed Extract) Inhibits Skin Aging Caused by Streptozotocin-Induced Glycation in Hairless Mice.","date":"2023","source":"Preventive nutrition and food science","url":"https://pubmed.ncbi.nlm.nih.gov/37416794","citation_count":10,"is_preprint":false},{"pmid":"30513865","id":"PMC_30513865","title":"High-Throughput Sequencing Reveals Cyclamen persicum Mill. as a Natural Host for Fig Mosaic Virus.","date":"2018","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/30513865","citation_count":10,"is_preprint":false},{"pmid":"21041977","id":"PMC_21041977","title":"Molecular phylogenies of figs and fig-pollinating wasps in the Ryukyu and Bonin (Ogasawara) islands, Japan.","date":"2010","source":"Genes & genetic systems","url":"https://pubmed.ncbi.nlm.nih.gov/21041977","citation_count":9,"is_preprint":false},{"pmid":"32567765","id":"PMC_32567765","title":"Low-coverage genomic data resolve the population divergence and gene flow history of an Australian rain forest fig wasp.","date":"2020","source":"Molecular ecology","url":"https://pubmed.ncbi.nlm.nih.gov/32567765","citation_count":9,"is_preprint":false},{"pmid":"22138987","id":"PMC_22138987","title":"Surveillance study of hepatitis A virus RNA on fig and date samples.","date":"2011","source":"Applied and environmental microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22138987","citation_count":9,"is_preprint":false},{"pmid":"22254099","id":"PMC_22254099","title":"Antioxidant activity of a Mediterranean food product: \"fig syrup\".","date":"2011","source":"Nutrients","url":"https://pubmed.ncbi.nlm.nih.gov/22254099","citation_count":8,"is_preprint":false},{"pmid":"32911158","id":"PMC_32911158","title":"Broad range of substrate specificities in papain and fig latex enzymes preparations improve enumeration of Listeria monocytogenes.","date":"2020","source":"International journal of food microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32911158","citation_count":8,"is_preprint":false},{"pmid":"33627966","id":"PMC_33627966","title":"Physiological and molecular responses for long term salinity stress in common fig (Ficus carica L.).","date":"2021","source":"Physiology and molecular biology of plants : an international journal of functional plant biology","url":"https://pubmed.ncbi.nlm.nih.gov/33627966","citation_count":8,"is_preprint":false},{"pmid":"36243214","id":"PMC_36243214","title":"Olfactory and gustatory receptor genes in fig wasps: Evolutionary insights from comparative studies.","date":"2022","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/36243214","citation_count":7,"is_preprint":false},{"pmid":"33838190","id":"PMC_33838190","title":"Gene duplication and subsequent functional diversification of maltase in fig wasp (Chalcidoidea, Hymenoptera).","date":"2021","source":"International journal of biological macromolecules","url":"https://pubmed.ncbi.nlm.nih.gov/33838190","citation_count":7,"is_preprint":false},{"pmid":"26739411","id":"PMC_26739411","title":"Papain Induced Occupational Asthma with Kiwi and Fig Allergy.","date":"2015","source":"Allergy, asthma & immunology research","url":"https://pubmed.ncbi.nlm.nih.gov/26739411","citation_count":7,"is_preprint":false},{"pmid":"35624846","id":"PMC_35624846","title":"Jelly Fig (Ficus awkeotsang Makino) Exhibits Antioxidative and Anti-Inflammatory Activities by Regulating Reactive Oxygen Species Production via NFκB Signaling Pathway.","date":"2022","source":"Antioxidants (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35624846","citation_count":7,"is_preprint":false},{"pmid":"30960143","id":"PMC_30960143","title":"Solubility Difference between Pectic Fractions from Creeping Fig Seeds.","date":"2019","source":"Polymers","url":"https://pubmed.ncbi.nlm.nih.gov/30960143","citation_count":7,"is_preprint":false},{"pmid":"27097639","id":"PMC_27097639","title":"Chlorophyll metabolism in pollinated vs. parthenocarpic fig fruits throughout development and ripening.","date":"2016","source":"Planta","url":"https://pubmed.ncbi.nlm.nih.gov/27097639","citation_count":7,"is_preprint":false},{"pmid":"30579922","id":"PMC_30579922","title":"Production of a polyclonal antiserum against recombinant nucleocapsid protein and its application for the detection of fig mosaic virus.","date":"2018","source":"Journal of virological methods","url":"https://pubmed.ncbi.nlm.nih.gov/30579922","citation_count":7,"is_preprint":false},{"pmid":"31812630","id":"PMC_31812630","title":"Generation and molecular docking analysis of specific single-chain variable fragments selected by phage display against the recombinant nucleocapsid protein of fig mosaic virus.","date":"2019","source":"Journal of virological methods","url":"https://pubmed.ncbi.nlm.nih.gov/31812630","citation_count":7,"is_preprint":false},{"pmid":"33203150","id":"PMC_33203150","title":"Evolution of Oxidative Phosphorylation (OXPHOS) Genes Reflecting the Evolutionary and Life Histories of Fig Wasps (Hymenoptera, Chalcidoidea).","date":"2020","source":"Genes","url":"https://pubmed.ncbi.nlm.nih.gov/33203150","citation_count":7,"is_preprint":false},{"pmid":"35595238","id":"PMC_35595238","title":"A chromosome-level genome assembly of the pollinating fig wasp Valisia javana.","date":"2022","source":"DNA research : an international journal for rapid publication of reports on genes and genomes","url":"https://pubmed.ncbi.nlm.nih.gov/35595238","citation_count":6,"is_preprint":false},{"pmid":"36388580","id":"PMC_36388580","title":"AP2/ERF genes associated with superfast fig (Ficus carica L.) fruit ripening.","date":"2022","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/36388580","citation_count":6,"is_preprint":false},{"pmid":"17691807","id":"PMC_17691807","title":"Purification, cloning, and identification of two thaumatin-like protein isoforms in jelly fig (Ficus awkeotsang) Achenes.","date":"2007","source":"Journal of agricultural and food chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17691807","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48274,"output_tokens":3079,"usd":0.095504},"stage2":{"model":"claude-opus-4-6","input_tokens":6428,"output_tokens":2708,"usd":0.14976},"total_usd":0.245264,"stage1_batch_id":"msgbatch_0118RScg3WGaGkaZRtWZbtce","stage2_batch_id":"msgbatch_01Cpfzvtbj42aqp5oYZ5Te2s","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2005,\n      \"finding\": \"DEPP (decidual protein induced by progesterone) was cloned from human endometrial stromal cell cDNA library; it increases phosphorylated ERK levels and activates the Elk-1 transcription factor in HEK293 cells, placing DEPP upstream of ERK/Elk-1 signaling during decidualization.\",\n      \"method\": \"Overexpression in HEK293 cells, ERK phosphorylation assay, Elk-1 reporter assay\",\n      \"journal\": \"Molecular human reproduction\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single overexpression experiment with functional readout but no mutagenesis or binding partner identification\",\n      \"pmids\": [\"16123073\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DEPP expression in human endothelial cells is transcriptionally regulated by FoxO transcription factors via two functional FoxO-responsive elements identified in the DEPP promoter; hypoxia-induced DEPP upregulation is FoxO-dependent.\",\n      \"method\": \"Reporter assay (DEPP promoter-luciferase), FoxO knockdown/overexpression, hypoxia treatment in EA.hy926 cells\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — promoter functional mapping plus genetic (siRNA) epistasis in two conditions\",\n      \"pmids\": [\"21510935\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DEPP localizes to peroxisomes and mitochondria in neuroblastoma cells via an N-terminal peroxisomal-targeting-signal-type-2 (PTS2) sequence; it directly binds the PEX7 peroxisomal import receptor (co-immunoprecipitation); DEPP overexpression reduces catalase activity and elevates ROS, while knockdown increases catalase activity and PPARG expression, establishing DEPP as an impairment of peroxisomal ROS detoxification.\",\n      \"method\": \"Confocal microscopy of EYFP-tagged DEPP with peroxisomal/mitochondrial probes, co-immunoprecipitation with PEX7, catalase activity assay, siRNA knockdown, conditional overexpression\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods (localization, co-IP, enzymatic assay, gain- and loss-of-function) in one study\",\n      \"pmids\": [\"25261981\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DEPP is a major hypoxia-inducible gene regulated by oxidative stress (EC-SOD); overexpressed DEPP co-localizes with protein aggregates/aggresomes and is rapidly degraded by the proteasome; DEPP overexpression activates autophagy, and DEPP silencing attenuates autophagy, linking DEPP to the autophagy pathway.\",\n      \"method\": \"Subcellular fractionation, immunofluorescence microscopy, proteasome inhibitor treatment, autophagy modulation (3-methyladenine, rapamycin), siRNA knockdown, EC-SOD overexpression mouse model\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods in one lab; orthogonal approaches for localization and autophagy phenotype\",\n      \"pmids\": [\"24530860\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"DEPP mediates FOXO3-induced autophagy in neuroblastoma by inducing ROS accumulation; DEPP knockdown is sufficient to block autophagy under serum starvation and genotoxic stress, and N-acetyl-cysteine (ROS scavenger) fully blocks DEPP-induced autophagosome formation, positioning ROS accumulation as the mechanistic link between DEPP and autophagy.\",\n      \"method\": \"Live-cell fluorescence microscopy (EYFP-LC3), immunoblot (LC3), ROS measurement (MitoTracker Red), siRNA knockdown of DEPP and LC3, N-acetyl-cysteine treatment, flow cytometry\",\n      \"journal\": \"Molecular cancer\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods, epistasis established by chemical rescue, replicated across stress conditions\",\n      \"pmids\": [\"28545464\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Ectopic DEPP expression in HCT116 colon cancer cells activates Ras/Raf/MEK/ERK and p16INK4A/Rb signaling pathways and induces cellular senescence (SA-β-Gal activity); DEPP knockdown counteracts drug-induced senescence, growth inhibition, and cell cycle arrest, establishing DEPP as a positive regulator of RAS/ERK-driven senescence.\",\n      \"method\": \"Ectopic overexpression, siRNA knockdown, SA-β-Gal assay, Western blot for pathway components, xenograft mouse model\",\n      \"journal\": \"Cell death & disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — gain- and loss-of-function with pathway readout and in vivo validation, single lab\",\n      \"pmids\": [\"29440765\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Hepatic overexpression of DEPP in mice promotes fatty acid oxidation and ketogenesis and suppresses lipogenesis and gluconeogenesis; DEPP increases hepatic ROS by impairing the ROS scavenging system; FGF21, upregulated in response to DEPP-induced oxidative stress, mediates the effects of DEPP on fatty acid oxidation, ketogenesis and lipid synthesis (but not gluconeogenesis), as shown by FGF21 antibody blockade.\",\n      \"method\": \"Adenovirus-mediated hepatic overexpression in mice, indirect calorimetry, biochemical assays (liver TG, glycogen, β-hydroxybutyrate), catalase activity assay, live-cell ROS fluorescence, qPCR, FGF21 antibody neutralization, db/db mouse model\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vivo overexpression with mechanistic dissection via antibody epistasis and multiple metabolic readouts\",\n      \"pmids\": [\"29702025\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"DEPP mRNA is highly expressed in white adipose tissue and is regulated by insulin: insulin treatment significantly decreases DEPP mRNA in 3T3-L1 adipocytes, rat H4IIE, and human HepG2 hepatoma cells; fasting induces and refeeding suppresses hepatic/adipose DEPP expression in vivo, identifying insulin as a negative regulator of DEPP.\",\n      \"method\": \"Northern blot, in vitro insulin treatment of multiple cell lines, in vivo fasting/refeeding experiments, streptozotocin-induced diabetic mouse model\",\n      \"journal\": \"Hormone and metabolic research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — replicated across multiple cell lines and in vivo models in one study\",\n      \"pmids\": [\"19937567\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"DEPP overexpression in HCT116 colon cancer cells promotes MAPK (ERK, JNK, p38) phosphorylation and upregulates Gadd45a; DEPP or Gadd45a knockdown impairs baicalein-induced apoptosis, caspase-3/9 activation, and MAPK phosphorylation; JNK/p38 inhibition decreases Gadd45a expression, establishing a DEPP→MAPK→Gadd45a positive feedback loop leading to apoptosis.\",\n      \"method\": \"siRNA knockdown of DEPP and Gadd45a, Annexin V/PI apoptosis assay, caspase activity assay, Western blot for phospho-MAPKs, kinase inhibitors (SP600125, SB203580, SCH772984)\",\n      \"journal\": \"International journal of oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — epistasis established with multiple inhibitors and siRNA, single lab\",\n      \"pmids\": [\"29749481\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"DEPP activates mitochondrial autophagy (mitophagy) in chondrocytes via BCL2 interacting protein 3 (BNIP3); DEPP is downstream of FOXO transcription factors in chondrocytes; DEPP knockout mice show exacerbated cartilage degradation with decreased autophagic flux and increased chondrocyte death, establishing DEPP as a stress-inducible regulator of mitophagy in osteoarthritis.\",\n      \"method\": \"DEPP knockdown/overexpression in chondrocytes, autophagic flux measurement, FOXO knockdown, subcellular fractionation, DEPP-knockout mice (destabilization of medial meniscus OA model), TUNEL assay\",\n      \"journal\": \"FASEB journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — in vivo knockout model combined with cell-based mechanistic studies and identification of BNIP3 as downstream effector\",\n      \"pmids\": [\"34997944\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"DEPP1 is induced by HIF (hypoxia-inducible factor) under hypoxia in cardiomyocytes; DEPP1 localizes inside mitochondria; DEPP1 is both necessary and sufficient for hypoxia-induced autophagy and triglyceride accumulation in cardiomyocytes; whole-body Depp1 knockout decreases cardiac dysfunction in mice with chronic HIF activation (VHL cardiac knockout), establishing DEPP1 as a key HIF-downstream mediator of ischemic cardiomyopathy features.\",\n      \"method\": \"CRISPR-Cas9 Depp1 knockout mice, cardiac pVHL-knockout mice, RNA sequencing, immunoblot, mitochondrial and peroxisomal autophagy flux measurements, live-cell imaging of isolated cardiomyocytes\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — in vivo CRISPR knockout with gain-of-function epistasis, multiple orthogonal methods including organelle-specific autophagy flux and cardiac phenotype\",\n      \"pmids\": [\"38881449\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DEPP1 (C10ORF10/DEPP) is a HIF- and FOXO3-transcriptional target that localizes to peroxisomes (via PTS2/PEX7) and mitochondria, where it impairs ROS detoxification by reducing catalase activity, thereby elevating cellular ROS that drive autophagy (including mitophagy via BNIP3), activate ERK/MAPK and senescence pathways, and induce FGF21-mediated metabolic reprogramming; in cardiac tissue, DEPP1 is necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation, making it a central mediator linking hypoxia/FOXO signaling to organelle quality control and metabolic disease.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"DEPP1 is a stress-inducible peroxisomal and mitochondrial protein that links hypoxia and FOXO3 signaling to organelle-selective autophagy and metabolic reprogramming by elevating cellular reactive oxygen species. It is transcriptionally induced by HIF and FOXO3 (and suppressed by insulin), localizes to peroxisomes via an N-terminal PTS2 signal recognized by the import receptor PEX7, and impairs catalase-dependent ROS detoxification; the resulting ROS accumulation drives autophagosome formation—including BNIP3-dependent mitophagy—as demonstrated by chemical rescue with N-acetyl-cysteine [PMID:25261981, PMID:28545464, PMID:34997944]. DEPP1-induced ROS also activate the Ras/Raf/MEK/ERK cascade, promoting cellular senescence and, in the liver, FGF21-dependent fatty acid oxidation and ketogenesis [PMID:29440765, PMID:29702025, PMID:29749481]. In cardiomyocytes, DEPP1 is both necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation, and whole-body Depp1 knockout ameliorates cardiac dysfunction in a mouse model of chronic HIF activation [PMID:38881449].\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"Initial cloning established that DEPP1 is not merely a decidualization marker but an active signaling molecule capable of engaging the ERK/Elk-1 pathway, raising the question of its upstream inputs and downstream consequences.\",\n      \"evidence\": \"Overexpression in HEK293 cells with ERK phosphorylation and Elk-1 reporter assays\",\n      \"pmids\": [\"16123073\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No endogenous loss-of-function data\", \"Mechanism of ERK activation unknown\", \"No binding partner or direct substrate identified\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Identification of insulin as a negative regulator and fasting as a positive regulator of DEPP1 expression placed the gene within nutrient-sensing circuitry, though the downstream metabolic consequences remained undefined.\",\n      \"evidence\": \"Northern blot across tissues and cell lines, fasting/refeeding and streptozotocin diabetic mouse models\",\n      \"pmids\": [\"19937567\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No mechanism linking insulin signaling to DEPP1 promoter\", \"Functional consequence of DEPP1 induction during fasting not tested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Mapping of two functional FoxO-responsive elements in the DEPP1 promoter resolved how hypoxia and stress transcriptionally upregulate the gene, establishing DEPP1 as a direct FOXO transcriptional target.\",\n      \"evidence\": \"Promoter-luciferase reporters with site mutagenesis, FoxO knockdown/overexpression under normoxia and hypoxia in EA.hy926 endothelial cells\",\n      \"pmids\": [\"21510935\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"HIF-responsive elements not yet mapped\", \"No chromatin immunoprecipitation to confirm direct FoxO occupancy\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Determining that DEPP1 localizes to peroxisomes via PTS2/PEX7 and to mitochondria, and that it impairs catalase activity to elevate ROS, provided the first mechanistic explanation for its cellular function and linked it to organelle-level redox control.\",\n      \"evidence\": \"Confocal microscopy of EYFP-tagged DEPP1, co-immunoprecipitation with PEX7, catalase activity assays, gain- and loss-of-function in neuroblastoma cells\",\n      \"pmids\": [\"25261981\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism by which DEPP1 inhibits catalase (direct binding vs. indirect) unclear\", \"Relative functional importance of peroxisomal vs. mitochondrial pools not resolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstration that DEPP1 overexpression activates autophagy and that silencing attenuates it established autophagy induction as a major downstream output, though the signaling intermediary (ROS) was not yet proven.\",\n      \"evidence\": \"Autophagy modulation with 3-methyladenine and rapamycin, siRNA knockdown, EC-SOD overexpression mouse model, proteasome inhibitor treatment\",\n      \"pmids\": [\"24530860\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal role of ROS in DEPP1-driven autophagy not directly tested\", \"Selectivity of autophagy (mitophagy vs. bulk) uncharacterized\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Chemical rescue with N-acetyl-cysteine proved that ROS accumulation is the obligate intermediary between DEPP1 and autophagosome formation, closing the mechanistic gap between peroxisomal catalase inhibition and autophagy activation.\",\n      \"evidence\": \"Live-cell LC3 imaging, ROS measurement, NAC rescue, siRNA epistasis across starvation and genotoxic stress in neuroblastoma cells\",\n      \"pmids\": [\"28545464\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Identity of the ROS sensor linking peroxisomal ROS to autophagy machinery unknown\", \"Whether mitophagy specifically requires DEPP1-ROS axis not tested\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Three studies collectively expanded the functional repertoire of DEPP1 beyond autophagy: hepatic DEPP1 drives FGF21-dependent fatty acid oxidation and ketogenesis; DEPP1 activates Ras/ERK to induce senescence; and a DEPP1→MAPK→Gadd45a feedback loop promotes apoptosis—all converging on ROS as the common upstream signal.\",\n      \"evidence\": \"Adenovirus-mediated hepatic overexpression with FGF21 antibody neutralization in mice; ectopic expression and siRNA in HCT116 with SA-β-Gal, MAPK blots, and kinase inhibitor epistasis; xenograft models\",\n      \"pmids\": [\"29702025\", \"29440765\", \"29749481\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"FGF21 mediates fatty acid oxidation but not gluconeogenesis effects—alternate pathway unidentified\", \"Direct physical interaction between DEPP1 and Ras/Raf components not established\", \"Relative contributions of ERK vs. JNK/p38 to different DEPP1 phenotypes unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"DEPP1 knockout mice with surgically induced osteoarthritis showed exacerbated cartilage degradation, establishing DEPP1 as a physiologically relevant stress-protective factor and identifying BNIP3 as the downstream effector coupling DEPP1 to mitophagy in chondrocytes.\",\n      \"evidence\": \"DEPP1-knockout mice with destabilized medial meniscus model, autophagic flux measurement, BNIP3 epistasis, TUNEL assay\",\n      \"pmids\": [\"34997944\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether BNIP3 upregulation is a direct ROS effect or requires transcriptional intermediaries unknown\", \"Peroxisomal autophagy contribution in chondrocytes not assessed\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"CRISPR knockout of Depp1 in mice demonstrated that DEPP1 is necessary and sufficient for HIF-induced mitochondrial and peroxisomal autophagy and triglyceride accumulation in cardiomyocytes, and that its loss ameliorates cardiac dysfunction under chronic HIF activation, positioning DEPP1 as a central mediator of ischemic cardiomyopathy pathology.\",\n      \"evidence\": \"Whole-body CRISPR-Cas9 Depp1 knockout crossed with cardiac VHL-knockout mice, organelle-specific autophagy flux, RNA-seq, live-cell imaging of cardiomyocytes\",\n      \"pmids\": [\"38881449\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mitochondrial import mechanism of DEPP1 not resolved\", \"Molecular basis of triglyceride accumulation downstream of DEPP1 not defined\", \"Whether cardiac phenotype rescue is cell-autonomous to cardiomyocytes not formally demonstrated with conditional knockout\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular mechanism by which DEPP1 inhibits catalase—whether through physical binding, post-translational modification, or displacement from peroxisomes—remains unresolved, as does the identity of the ROS sensor that couples DEPP1-elevated ROS to autophagy initiation machinery.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural or biochemical reconstitution of DEPP1-catalase interaction\", \"ROS sensor or adaptor linking peroxisomal ROS to autophagosome nucleation unknown\", \"Tissue-specific differences in DEPP1 function (cardiac vs. hepatic vs. chondrocyte) not mechanistically explained\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 4, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005777\", \"supporting_discovery_ids\": [2, 10]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [2, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [3, 4, 9, 10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [0, 5, 8]},\n      {\"term_id\": \"R-HSA-8953897\", \"supporting_discovery_ids\": [1, 2, 4, 6]},\n      {\"term_id\": \"R-HSA-1430728\", \"supporting_discovery_ids\": [6, 7]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PEX7\", \"BNIP3\", \"FGF21\", \"GADD45A\"],\n    \"other_free_text\": []\n  }\n}\n```"}