{"gene":"DYNLT3","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2007,"finding":"DYNLT3 directly binds to Bub3, a spindle checkpoint protein; Bub3 binds exclusively to DYNLT3 and not to other dynein light chains, linking cytoplasmic dynein to the spindle checkpoint complex through DYNLT3.","method":"GST pull-down assay and co-immunoprecipitation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down, two orthogonal methods in a single focused study establishing exclusivity of the interaction","pmids":["17289665"],"is_preprint":false},{"year":2007,"finding":"DYNLT3 localizes to kinetochores at prometaphase but is depleted from kinetochores during chromosome alignment, mirroring the behavior of Bub3 and other spindle checkpoint proteins.","method":"Immunofluorescence microscopy of mitotic cells","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization experiment in a single lab, single method, but clear functional context","pmids":["17289665"],"is_preprint":false},{"year":2007,"finding":"siRNA knockdown of DYNLT3 increases the mitotic index, particularly increasing the number of cells in prophase/prometaphase, consistent with a role for DYNLT3 in chromosome congression and transport of checkpoint proteins from kinetochore to spindle pole.","method":"siRNA knockdown with mitotic index quantification by immunofluorescence","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KD with defined cellular phenotype in a single lab, single method","pmids":["17289665"],"is_preprint":false},{"year":2011,"finding":"DYNLT3 localizes to the germinal vesicle and kinetochores during mouse oocyte meiosis (GVBD, metaphase I and II); antibody-mediated depletion causes chromosome misalignment, kinetochore-microtubule detachment, decreased polar body extrusion, and inhibition of homologous chromosome segregation at meiosis I.","method":"Immunofluorescent staining for localization; antibody injection for depletion with chromosome-spread and spindle assembly readouts in mouse oocytes","journal":"Reproductive sciences","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct localization and loss-of-function with multiple phenotypic readouts, single lab","pmids":["21693773"],"is_preprint":false},{"year":2021,"finding":"In melanocytes, Dynlt3 (a cytoplasmic dynein component) is required for efficient melanosome transport, acidity, and transfer to keratinocytes; knockdown causes more directional melanosome motion leading to peripheral positioning, increased acidity of stage IV melanosomes, and less efficient melanosome transfer.","method":"Live-cell imaging/motion analysis, pH measurements, transfer assays in Dynlt3-knockdown mouse melanocytes","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal functional assays (motility tracking, acidity, transfer) in a single focused study","pmids":["33772156"],"is_preprint":false},{"year":2021,"finding":"The level of Dynlt3 in melanocytes is regulated by β-catenin (Wnt/β-catenin signalling pathway), coupling melanosome transport/positioning/acidity to Wnt signalling.","method":"β-catenin activity modulation with Western blot measurement of Dynlt3 levels in mouse melanocytes","journal":"Communications biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (Western blot after pathway modulation), no mutagenesis or direct binding assay","pmids":["33772156"],"is_preprint":false},{"year":2022,"finding":"Overexpression of DYNLT3 in cervical cancer cells decreases expression of Wnt pathway proteins (Dvl2, Dvl3, p-LRP6, Wnt3a, Wnt5a/b, Naked1/2, β-catenin, C-Myc) and EMT markers (N-cadherin, SOX2, OCT4, vimentin, Snail) while increasing E-cadherin and Axin1, suppressing proliferation, migration, invasion, and promoting apoptosis; knockdown produces opposite effects.","method":"Western blotting, CCK-8, BrdU, colony formation, FACS, wound healing, Transwell assays, and nude mouse xenograft model","journal":"Frontiers in oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple cellular assays and in vivo model from a single lab; pathway placement via protein-level readouts but no direct binding or reconstitution","pmids":["35965516"],"is_preprint":false},{"year":2023,"finding":"DYNLT3 knockdown in breast cancer cells (MDA-MB-231, MCF-7) elevates N-cadherin and vimentin and reduces E-cadherin (promoting EMT), while suppressing proliferation, migration, and invasion; overexpression reverses these effects, placing DYNLT3 upstream of EMT regulation.","method":"siRNA knockdown and overexpression with Western blot, CCK-8, BrdU, colony formation, wound healing, Transwell, flow cytometry, and nude mouse xenograft","journal":"Cancer medicine","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal cell-based and in vivo assays, single lab, no direct mechanistic binding data","pmids":["37260179"],"is_preprint":false}],"current_model":"DYNLT3 is a cytoplasmic dynein light chain that confers cargo-binding specificity by directly and exclusively linking the dynein complex to the spindle checkpoint protein Bub3, localizes to kinetochores during prometaphase to support chromosome congression and spindle checkpoint signalling, and is required for melanosome transport, acidity, and transfer in melanocytes; additionally, DYNLT3 modulates EMT-related and Wnt/β-catenin pathway proteins in several cancer cell contexts."},"narrative":{"mechanistic_narrative":"DYNLT3 is a cytoplasmic dynein light chain that confers cargo-binding specificity, coupling the dynein motor to distinct intracellular transport and signalling functions [PMID:17289665, PMID:33772156]. It directly and exclusively binds the spindle checkpoint protein Bub3 — an interaction not shared by other dynein light chains — thereby linking cytoplasmic dynein to the spindle assembly checkpoint [PMID:17289665]. Consistent with this role, DYNLT3 localizes to kinetochores at prometaphase and is depleted upon chromosome alignment, mirroring Bub3, and its loss elevates the mitotic index with accumulation in prophase/prometaphase, indicating a function in chromosome congression and the transport of checkpoint proteins from kinetochore to spindle pole [PMID:17289665]. The same kinetochore role extends to meiosis, where DYNLT3 depletion in oocytes causes chromosome misalignment, kinetochore-microtubule detachment, and impaired homologous chromosome segregation [PMID:21693773]. In a separate transport context, DYNLT3 is required in melanocytes for efficient melanosome transport, regulation of melanosome acidity, and transfer to keratinocytes [PMID:33772156]. DYNLT3 also acts as a regulator of EMT and Wnt/β-catenin pathway proteins in cervical and breast cancer cells, where it suppresses proliferation, migration, and invasion [PMID:35965516, PMID:37260179].","teleology":[{"year":2007,"claim":"Established how cytoplasmic dynein is physically coupled to the spindle checkpoint by identifying DYNLT3 as the exclusive light-chain link to Bub3, and showed this link operates at kinetochores during mitosis.","evidence":"GST pull-down and reciprocal co-immunoprecipitation for binding; immunofluorescence localization and siRNA knockdown with mitotic-index quantification for function","pmids":["17289665"],"confidence":"High","gaps":["Whether DYNLT3 physically tethers Bub3 to an intact dynein motor in a reconstituted system is not shown","The structural basis of Bub3 exclusivity for DYNLT3 over other light chains is undefined","Direct demonstration that DYNLT3-dependent dynein actively strips checkpoint proteins to the spindle pole is not provided"]},{"year":2011,"claim":"Extended the kinetochore role of DYNLT3 from mitosis to meiosis, establishing its requirement for chromosome alignment and segregation in oocytes.","evidence":"Immunofluorescent localization and antibody-mediated depletion with chromosome-spread and spindle readouts in mouse oocytes","pmids":["21693773"],"confidence":"Medium","gaps":["Whether the meiotic phenotype depends on the DYNLT3-Bub3 interaction was not tested","Single-lab, antibody-injection approach without genetic confirmation"]},{"year":2021,"claim":"Defined a distinct cargo-transport role for DYNLT3 in melanocytes, linking it to melanosome positioning, acidity, and transfer, and connecting its expression to Wnt/β-catenin signalling.","evidence":"Live-cell motion analysis, pH measurements, and transfer assays in knockdown melanocytes; β-catenin modulation with Western blot of Dynlt3 levels","pmids":["33772156"],"confidence":"Medium","gaps":["The β-catenin regulation of Dynlt3 rests on a single Western-blot readout without direct promoter or binding evidence","The identity of the melanosomal cargo adaptor engaged by DYNLT3 is unknown","Mechanism linking dynein-driven transport to melanosome acidity is not resolved"]},{"year":2023,"claim":"Positioned DYNLT3 as a regulator of EMT and Wnt/β-catenin pathway proteins in cancer, where its level inversely controls proliferation, migration, and invasion.","evidence":"Knockdown and overexpression with Western blotting of pathway/EMT markers plus proliferation, migration, invasion, apoptosis assays and nude-mouse xenografts in cervical and breast cancer cells","pmids":["35965516","37260179"],"confidence":"Medium","gaps":["Pathway placement rests on protein-level readouts without direct binding or reconstitution","How a dynein light chain mechanistically modulates Wnt components is undefined","Whether the cancer effects require dynein motor function or the Bub3 interaction is untested"]},{"year":null,"claim":"It remains unknown how a single dynein light chain mechanistically reconciles its kinetochore/checkpoint role, its melanosome transport role, and its modulation of Wnt/EMT signalling.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model of DYNLT3 within the dynein complex or with cargo adaptors","No unifying biochemical mechanism linking the distinct cellular contexts","Direct cargo specificity determinants beyond Bub3 are uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[1,3]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,4]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[1,2]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[4]}],"complexes":["cytoplasmic dynein"],"partners":["BUB3"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"P51808","full_name":"Dynein light chain Tctex-type 3","aliases":["Protein 91/23","T-complex-associated testis-expressed 1-like"],"length_aa":116,"mass_kda":13.1,"function":"Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. Probably binds BUB3 as part of transport cargo. Required for the efficient progression through mitosis (By similarity)","subcellular_location":"Nucleus; Cytoplasm, cytoskeleton; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/P51808/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DYNLT3","classification":"Not Classified","n_dependent_lines":8,"n_total_lines":1208,"dependency_fraction":0.006622516556291391},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"DYNC1I2","stoichiometry":10.0},{"gene":"DYNC1LI1","stoichiometry":10.0},{"gene":"DYNLL1","stoichiometry":4.0}],"url":"https://opencell.sf.czbiohub.org/search/DYNLT3","total_profiled":1310},"omim":[{"mim_id":"617353","title":"DYNEIN, LIGHT CHAIN, TCTEX-TYPE, 2B; DYNLT2B","url":"https://www.omim.org/entry/617353"},{"mim_id":"300302","title":"DYNEIN, LIGHT CHAIN, TCTEX TYPE, 3; DYNLT3","url":"https://www.omim.org/entry/300302"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DYNLT3"},"hgnc":{"alias_symbol":["TCTEX1L"],"prev_symbol":["TCTE1L"]},"alphafold":{"accession":"P51808","domains":[{"cath_id":"3.30.1140.40","chopping":"14-112","consensus_level":"high","plddt":96.5841,"start":14,"end":112}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P51808","model_url":"https://alphafold.ebi.ac.uk/files/AF-P51808-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P51808-F1-predicted_aligned_error_v6.png","plddt_mean":91.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DYNLT3","jax_strain_url":"https://www.jax.org/strain/search?query=DYNLT3"},"sequence":{"accession":"P51808","fasta_url":"https://rest.uniprot.org/uniprotkb/P51808.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P51808/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P51808"}},"corpus_meta":[{"pmid":"17289665","id":"PMC_17289665","title":"The DYNLT3 light chain directly links cytoplasmic dynein to a spindle checkpoint protein, Bub3.","date":"2007","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17289665","citation_count":40,"is_preprint":false},{"pmid":"21693773","id":"PMC_21693773","title":"DYNLT3 is required for chromosome alignment during mouse oocyte meiotic maturation.","date":"2011","source":"Reproductive sciences (Thousand Oaks, Calif.)","url":"https://pubmed.ncbi.nlm.nih.gov/21693773","citation_count":18,"is_preprint":false},{"pmid":"35965516","id":"PMC_35965516","title":"DYNLT3 overexpression induces apoptosis and inhibits cell growth and migration via inhibition of the Wnt pathway and EMT in cervical cancer.","date":"2022","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/35965516","citation_count":10,"is_preprint":false},{"pmid":"33772156","id":"PMC_33772156","title":"A role for Dynlt3 in melanosome movement, distribution, acidity and transfer.","date":"2021","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/33772156","citation_count":9,"is_preprint":false},{"pmid":"32964959","id":"PMC_32964959","title":"MicroRNA-1-3p inhibits the growth and metastasis of ovarian cancer cells by targeting DYNLT3.","date":"2020","source":"European review for medical and pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32964959","citation_count":8,"is_preprint":false},{"pmid":"37260179","id":"PMC_37260179","title":"The role of DYNLT3 in breast cancer proliferation, migration, and invasion via epithelial-to-mesenchymal transition.","date":"2023","source":"Cancer medicine","url":"https://pubmed.ncbi.nlm.nih.gov/37260179","citation_count":6,"is_preprint":false},{"pmid":"12559582","id":"PMC_12559582","title":"Comparative analysis, gene organization and expression of canine TCTE1L.","date":"2003","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/12559582","citation_count":1,"is_preprint":false},{"pmid":"12844343","id":"PMC_12844343","title":"Characterization of two labor-induced genes, DSCR1 and TCTE1L, in the pregnant ovine myometrium.","date":"2003","source":"The Journal of endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/12844343","citation_count":1,"is_preprint":false},{"pmid":"42166936","id":"PMC_42166936","title":"Integrated multi-omics and experimental validation reveal DYNLT3 as a tumor suppressor regulated by quercetin in lung squamous cell carcinoma.","date":"2026","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/42166936","citation_count":0,"is_preprint":false},{"pmid":"39868367","id":"PMC_39868367","title":"Corrigendum: DYNLT3 overexpression induces apoptosis and inhibits cell growth and migration via inhibition of the Wnt pathway and EMT in cervical cancer.","date":"2025","source":"Frontiers in oncology","url":"https://pubmed.ncbi.nlm.nih.gov/39868367","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7166,"output_tokens":1807,"usd":0.024302,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8733,"output_tokens":2235,"usd":0.04977,"stage2_stop_reason":"end_turn"},"total_usd":0.074072,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"DYNLT3 directly binds to Bub3, a spindle checkpoint protein; Bub3 binds exclusively to DYNLT3 and not to other dynein light chains, linking cytoplasmic dynein to the spindle checkpoint complex through DYNLT3.\",\n      \"method\": \"GST pull-down assay and co-immunoprecipitation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and GST pull-down, two orthogonal methods in a single focused study establishing exclusivity of the interaction\",\n      \"pmids\": [\"17289665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"DYNLT3 localizes to kinetochores at prometaphase but is depleted from kinetochores during chromosome alignment, mirroring the behavior of Bub3 and other spindle checkpoint proteins.\",\n      \"method\": \"Immunofluorescence microscopy of mitotic cells\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization experiment in a single lab, single method, but clear functional context\",\n      \"pmids\": [\"17289665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"siRNA knockdown of DYNLT3 increases the mitotic index, particularly increasing the number of cells in prophase/prometaphase, consistent with a role for DYNLT3 in chromosome congression and transport of checkpoint proteins from kinetochore to spindle pole.\",\n      \"method\": \"siRNA knockdown with mitotic index quantification by immunofluorescence\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KD with defined cellular phenotype in a single lab, single method\",\n      \"pmids\": [\"17289665\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"DYNLT3 localizes to the germinal vesicle and kinetochores during mouse oocyte meiosis (GVBD, metaphase I and II); antibody-mediated depletion causes chromosome misalignment, kinetochore-microtubule detachment, decreased polar body extrusion, and inhibition of homologous chromosome segregation at meiosis I.\",\n      \"method\": \"Immunofluorescent staining for localization; antibody injection for depletion with chromosome-spread and spindle assembly readouts in mouse oocytes\",\n      \"journal\": \"Reproductive sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct localization and loss-of-function with multiple phenotypic readouts, single lab\",\n      \"pmids\": [\"21693773\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"In melanocytes, Dynlt3 (a cytoplasmic dynein component) is required for efficient melanosome transport, acidity, and transfer to keratinocytes; knockdown causes more directional melanosome motion leading to peripheral positioning, increased acidity of stage IV melanosomes, and less efficient melanosome transfer.\",\n      \"method\": \"Live-cell imaging/motion analysis, pH measurements, transfer assays in Dynlt3-knockdown mouse melanocytes\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal functional assays (motility tracking, acidity, transfer) in a single focused study\",\n      \"pmids\": [\"33772156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"The level of Dynlt3 in melanocytes is regulated by β-catenin (Wnt/β-catenin signalling pathway), coupling melanosome transport/positioning/acidity to Wnt signalling.\",\n      \"method\": \"β-catenin activity modulation with Western blot measurement of Dynlt3 levels in mouse melanocytes\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (Western blot after pathway modulation), no mutagenesis or direct binding assay\",\n      \"pmids\": [\"33772156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Overexpression of DYNLT3 in cervical cancer cells decreases expression of Wnt pathway proteins (Dvl2, Dvl3, p-LRP6, Wnt3a, Wnt5a/b, Naked1/2, β-catenin, C-Myc) and EMT markers (N-cadherin, SOX2, OCT4, vimentin, Snail) while increasing E-cadherin and Axin1, suppressing proliferation, migration, invasion, and promoting apoptosis; knockdown produces opposite effects.\",\n      \"method\": \"Western blotting, CCK-8, BrdU, colony formation, FACS, wound healing, Transwell assays, and nude mouse xenograft model\",\n      \"journal\": \"Frontiers in oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple cellular assays and in vivo model from a single lab; pathway placement via protein-level readouts but no direct binding or reconstitution\",\n      \"pmids\": [\"35965516\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"DYNLT3 knockdown in breast cancer cells (MDA-MB-231, MCF-7) elevates N-cadherin and vimentin and reduces E-cadherin (promoting EMT), while suppressing proliferation, migration, and invasion; overexpression reverses these effects, placing DYNLT3 upstream of EMT regulation.\",\n      \"method\": \"siRNA knockdown and overexpression with Western blot, CCK-8, BrdU, colony formation, wound healing, Transwell, flow cytometry, and nude mouse xenograft\",\n      \"journal\": \"Cancer medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal cell-based and in vivo assays, single lab, no direct mechanistic binding data\",\n      \"pmids\": [\"37260179\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DYNLT3 is a cytoplasmic dynein light chain that confers cargo-binding specificity by directly and exclusively linking the dynein complex to the spindle checkpoint protein Bub3, localizes to kinetochores during prometaphase to support chromosome congression and spindle checkpoint signalling, and is required for melanosome transport, acidity, and transfer in melanocytes; additionally, DYNLT3 modulates EMT-related and Wnt/β-catenin pathway proteins in several cancer cell contexts.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DYNLT3 is a cytoplasmic dynein light chain that confers cargo-binding specificity, coupling the dynein motor to distinct intracellular transport and signalling functions [#0, #4]. It directly and exclusively binds the spindle checkpoint protein Bub3 — an interaction not shared by other dynein light chains — thereby linking cytoplasmic dynein to the spindle assembly checkpoint [#0]. Consistent with this role, DYNLT3 localizes to kinetochores at prometaphase and is depleted upon chromosome alignment, mirroring Bub3, and its loss elevates the mitotic index with accumulation in prophase/prometaphase, indicating a function in chromosome congression and the transport of checkpoint proteins from kinetochore to spindle pole [#1, #2]. The same kinetochore role extends to meiosis, where DYNLT3 depletion in oocytes causes chromosome misalignment, kinetochore-microtubule detachment, and impaired homologous chromosome segregation [#3]. In a separate transport context, DYNLT3 is required in melanocytes for efficient melanosome transport, regulation of melanosome acidity, and transfer to keratinocytes [#4]. DYNLT3 also acts as a regulator of EMT and Wnt/\\u03b2-catenin pathway proteins in cervical and breast cancer cells, where it suppresses proliferation, migration, and invasion [#6, #7].\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Established how cytoplasmic dynein is physically coupled to the spindle checkpoint by identifying DYNLT3 as the exclusive light-chain link to Bub3, and showed this link operates at kinetochores during mitosis.\",\n      \"evidence\": \"GST pull-down and reciprocal co-immunoprecipitation for binding; immunofluorescence localization and siRNA knockdown with mitotic-index quantification for function\",\n      \"pmids\": [\"17289665\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether DYNLT3 physically tethers Bub3 to an intact dynein motor in a reconstituted system is not shown\",\n        \"The structural basis of Bub3 exclusivity for DYNLT3 over other light chains is undefined\",\n        \"Direct demonstration that DYNLT3-dependent dynein actively strips checkpoint proteins to the spindle pole is not provided\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Extended the kinetochore role of DYNLT3 from mitosis to meiosis, establishing its requirement for chromosome alignment and segregation in oocytes.\",\n      \"evidence\": \"Immunofluorescent localization and antibody-mediated depletion with chromosome-spread and spindle readouts in mouse oocytes\",\n      \"pmids\": [\"21693773\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the meiotic phenotype depends on the DYNLT3-Bub3 interaction was not tested\",\n        \"Single-lab, antibody-injection approach without genetic confirmation\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defined a distinct cargo-transport role for DYNLT3 in melanocytes, linking it to melanosome positioning, acidity, and transfer, and connecting its expression to Wnt/\\u03b2-catenin signalling.\",\n      \"evidence\": \"Live-cell motion analysis, pH measurements, and transfer assays in knockdown melanocytes; \\u03b2-catenin modulation with Western blot of Dynlt3 levels\",\n      \"pmids\": [\"33772156\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The \\u03b2-catenin regulation of Dynlt3 rests on a single Western-blot readout without direct promoter or binding evidence\",\n        \"The identity of the melanosomal cargo adaptor engaged by DYNLT3 is unknown\",\n        \"Mechanism linking dynein-driven transport to melanosome acidity is not resolved\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Positioned DYNLT3 as a regulator of EMT and Wnt/\\u03b2-catenin pathway proteins in cancer, where its level inversely controls proliferation, migration, and invasion.\",\n      \"evidence\": \"Knockdown and overexpression with Western blotting of pathway/EMT markers plus proliferation, migration, invasion, apoptosis assays and nude-mouse xenografts in cervical and breast cancer cells\",\n      \"pmids\": [\"35965516\", \"37260179\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Pathway placement rests on protein-level readouts without direct binding or reconstitution\",\n        \"How a dynein light chain mechanistically modulates Wnt components is undefined\",\n        \"Whether the cancer effects require dynein motor function or the Bub3 interaction is untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown how a single dynein light chain mechanistically reconciles its kinetochore/checkpoint role, its melanosome transport role, and its modulation of Wnt/EMT signalling.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model of DYNLT3 within the dynein complex or with cargo adaptors\",\n        \"No unifying biochemical mechanism linking the distinct cellular contexts\",\n        \"Direct cargo specificity determinants beyond Bub3 are uncharacterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [1, 3]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\"cytoplasmic dynein\"],\n    \"partners\": [\"BUB3\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}