Affinage

TACC1

Transforming acidic coiled-coil-containing protein 1 · UniProt O75410

Length
805 aa
Mass
87.8 kDa
Annotated
2026-04-28
20 papers in source corpus 9 papers cited in narrative 9 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TACC1 is a multifunctional scaffold protein that operates at the intersection of microtubule regulation, mitotic progression, and nuclear receptor-mediated transcription. Its conserved C-terminal TACC domain confers microtubule plus-end tracking activity and is required for normal microtubule growth speed, while during mitosis and cytokinesis TACC1 forms cell-cycle-stage-specific complexes with ch-TOG, Aurora A, and Aurora B kinases at the spindle midzone and midbody, and its depletion perturbs cell division (PMID:26012630, PMID:14603251, PMID:15064709). In interphase, TACC1 resides in the chromatin-enriched nuclear fraction where it associates with unliganded thyroid hormone and retinoic acid receptors to sustain ligand-dependent transcriptional activation and proper nuclear retention of these receptors (PMID:20078863). TACC1 additionally interacts with Sm-like mRNA processing factors LSM7 and SmG, and constitutive overexpression transforms fibroblasts, linking its scaffolding functions to proliferative control (PMID:12165861, PMID:10435627).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1999 Medium

    Establishing that TACC1 possesses oncogenic potential answered whether this novel gene contributes to cell proliferation control.

    Evidence CMV-driven overexpression in mouse fibroblasts caused transformation and anchorage-independent growth

    PMID:10435627

    Open questions at the time
    • No downstream effector pathway identified
    • Transformation assay in single cell type only
    • Mechanism of oncogenic activity unknown
  2. 2002 Medium

    Identification of TACC1's physical interactors — mRNA-processing Sm-like proteins (LSM7, SmG), ch-TOG, and GAS41 — established that TACC1 participates in multiple distinct molecular complexes spanning mRNA homeostasis and microtubule regulation.

    Evidence Yeast two-hybrid screens, GST pull-downs, co-immunoprecipitation, and immunofluorescence in human cells

    PMID:11903063 PMID:12165861

    Open questions at the time
    • Functional significance of LSM7/SmG interaction not tested by loss-of-function
    • Direct versus bridged nature of GAS41 interaction not resolved
    • No in vivo confirmation of complex stoichiometry
  3. 2003 Medium

    Demonstrating that TACC1 resides in a mitotic complex with ch-TOG, Aurora A, TRAP, and LSM7, and that TACC1/ch-TOG depletion perturbs cell division, placed TACC1 as a functional component of the mitotic spindle machinery.

    Evidence Co-immunoprecipitation of complex members; siRNA knockdown with cell division phenotype readout

    PMID:14603251

    Open questions at the time
    • Aurora A phosphorylation of TACC1 not directly demonstrated
    • Relative contribution of TACC1 versus ch-TOG to the cell division defect not separated
    • Complex assembly dynamics during mitosis not characterized
  4. 2004 High

    Mapping TACC1 to the spindle midzone/midbody and showing its Aurora B-dependent localization and cytokinesis requirement resolved how TACC1 functions in late mitosis and demonstrated cell-cycle-stage-specific Aurora kinase partnerships.

    Evidence Immunofluorescence across cell cycle; TACC1–Aurora B co-IP during cytokinesis; Aurora B siRNA causing multinucleation and TACC1 mislocalization

    PMID:15064709

    Open questions at the time
    • Whether Aurora B directly phosphorylates TACC1 or recruits it indirectly is unknown
    • Nucleolar interphase function of TACC1 not explored
    • Phenotypic specificity of TACC1 depletion during cytokinesis not tested
  5. 2010 High

    Revealing that TACC1 binds unliganded nuclear receptors (TR, RAR) in the chromatin fraction and is required for their ligand-dependent transcriptional activity and nuclear retention established a second major function as a nuclear receptor coregulator, distinct from its cytoskeletal role.

    Evidence Y2H, GST pull-down, co-IP, nuclear fractionation, siRNA depletion with transcriptional reporter and receptor localization readouts in F9 cells

    PMID:20078863

    Open questions at the time
    • Whether TACC1 coregulator function extends to other nuclear receptor families is untested
    • Structural basis of TACC1–receptor interaction not resolved
    • How TACC1 simultaneously participates in cytoskeletal and nuclear functions (dual-use regulation) is unclear
  6. 2015 High

    Live imaging of Xenopus TACC1 as a bona fide microtubule plus-end tracker dependent on its TACC domain, with quantitative effects on microtubule growth speed, provided the first direct mechanistic evidence for TACC1 in microtubule dynamics regulation.

    Evidence Live-cell imaging of tagged TACC1, domain-deletion mapping, morpholino knockdown with microtubule dynamics measurements in Xenopus embryonic mesenchymal cells

    PMID:26012630

    Open questions at the time
    • Whether human TACC1 has identical +TIP behavior not confirmed in mammalian cells
    • Molecular basis of TACC domain plus-end recognition (e.g., EB1 dependence) not determined
    • Functional redundancy with TACC3 complicates single-gene loss-of-function interpretations
  7. 2021 Medium

    Showing that a specific TACC1 isoform (v25) suppresses proliferation and promotes autophagy via inhibition of pERK and mTOR signaling demonstrated isoform-specific pathway modulation and positioned TACC1 upstream of AKT/mTOR.

    Evidence Overexpression of TACC1v25 in HNSCC cells; western blot for pathway markers; pharmacological rescue with AKT activator SC79

    PMID:34897285

    Open questions at the time
    • Single overexpression study without endogenous isoform-specific depletion
    • Mechanism by which TACC1v25 suppresses pERK/mTOR not identified
    • Generalizability beyond HNSCC cell lines not tested
  8. 2022 Medium

    Identification of TACC1 as a direct miR-4742-5p target regulated by LINC01140 ceRNA activity in NSCLC placed TACC1 expression under post-transcriptional lncRNA/miRNA control linked to invasion and chemoresistance phenotypes.

    Evidence Luciferase reporter assay and RNA immunoprecipitation confirming miRNA binding; invasion and drug resistance assays in NSCLC cells

    PMID:35307914

    Open questions at the time
    • Whether miR-4742-5p regulation of TACC1 operates in non-cancer contexts is unknown
    • Downstream effectors mediating TACC1's role in invasion not identified
    • Single-lab study without in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TACC1 coordinates its dual cytoskeletal and nuclear coregulator functions — including whether these are mutually exclusive or regulated by post-translational modification, isoform switching, or cell-cycle gating — remains an open mechanistic question.
  • No structural model of TACC1 or its TACC domain bound to partners exists
  • Aurora A and Aurora B phosphorylation sites on TACC1 have not been mapped
  • In vivo genetic models for TACC1 function are lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 1
Localization
GO:0005856 cytoskeleton 2 GO:0005634 nucleus 1 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
AURKAAURKBCKAP5GAS41LSM7RARASNRPG
Complex memberships
TACC1–Aurora B cytokinesis complexch-TOG–TACC1–Aurora A mitotic complex

Evidence

Reading pass · 9 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Constitutive overexpression of TACC1 in mouse fibroblasts results in cellular transformation and anchorage-independent growth, indicating TACC1 has oncogenic/proliferative activity when inappropriately expressed. CMV-driven constitutive expression in mouse fibroblasts; transformation assay and anchorage-independent growth assay Oncogene Medium 10435627
2002 TACC1 protein is cytoplasmic and mainly perinuclear in localization, and interacts with the mRNA processing factors LSM7 and SmG (conserved Sm-like proteins associated with U6 snRNPs), suggesting a role in mRNA homeostasis. Immunofluorescence/subcellular fractionation; yeast two-hybrid screen, GST pull-down, and co-immunoprecipitation Oncogene Medium 12165861
2002 TACC1 interacts with the C-terminus of the microtubule-associated protein ch-TOG and with the oncogenic transcription factor GAS41/NuBI1, suggesting TACC1 participates in multiple distinct protein complexes. Yeast two-hybrid screen of human mammary epithelial cDNA library using full-length TACC1 as bait; confirmed by interaction mapping The Biochemical journal Medium 11903063
2003 TACC1 forms a protein complex with ch-TOG, Aurora A kinase, the adaptor protein TRAP, and the mRNA regulator LSM7; siRNA depletion of ch-TOG and TACC1 perturbs cell division, placing TACC1 in a mitotic regulatory complex. Co-immunoprecipitation to define complex members; siRNA knockdown with cell division phenotype readout Oncogene Medium 14603251
2004 TACC1 localizes to the midzone spindle in anaphase and strongly to the midbody during cytokinesis, then relocalizes to the nucleolus in interphase; TACC1 and Aurora B kinase form a complex specifically during cytokinesis; Aurora B knockdown prevents midbody formation, mislocalizes TACC1, and causes multinucleated cells. Immunofluorescence localization across cell cycle stages; co-immunoprecipitation of TACC1–Aurora B complex; siRNA knockdown of Aurora B with phenotypic readout (multinucleated cells) Oncogene High 15064709
2010 TACC1 interacts preferentially with unliganded Thyroid Hormone Receptors (TR) and Retinoic Acid Receptors (RAR); endogenous TACC1 localizes to the chromatin-enriched nuclear fraction in F9 cells and co-immunoprecipitates with RARα; TACC1 depletion reduces RAR and TR ligand-dependent transcriptional activity and causes TR to mislocalize from nucleus to cytoplasm, indicating TACC1 acts as a nuclear receptor coregulator/scaffold. Yeast two-hybrid screen; GST pull-down; colocalization; co-immunoprecipitation; nuclear fractionation; siRNA depletion with transcriptional activity and localization readouts BMC molecular biology High 20078863
2015 Xenopus TACC1 (ortholog of human TACC1) functions as a microtubule plus-end tracking protein (+TIP); the conserved C-terminal TACC domain is required for plus-end localization; TACC1 is required for normal microtubule growth speed in embryonic mesenchymal cells and shows partial functional redundancy with TACC3 in regulating microtubule growth lifetime. Live-cell imaging of fluorescently tagged TACC1; domain-deletion constructs to map +TIP localization; morpholino knockdown with microtubule dynamics measurements in Xenopus laevis embryonic cells Cytoskeleton (Hoboken, N.J.) High 26012630
2022 TACC1 is a target of miR-4742-5p; the lncRNA LINC01140 acts as a competing endogenous RNA (ceRNA) that sponges miR-4742-5p to relieve repression of TACC1 expression in NSCLC cells; reducing TACC1 (via miR-4742-5p) promotes invasion and cisplatin resistance. Luciferase reporter assay and RNA immunoprecipitation to confirm miR-4742-5p binding to TACC1 3'UTR and LINC01140; transwell invasion, flow cytometry apoptosis, and CCK-8 assays Journal of biochemical and molecular toxicology Medium 35307914
2021 Overexpression of TACC1 variant 25 (TACC1v25) in head and neck squamous carcinoma cells inhibits proliferation and promotes autophagy through suppression of nuclear pERK and p-mTOR signaling and upregulation of Beclin-1/LC3II; AKT pathway activation rescues autophagy suppression, placing TACC1v25 upstream of AKT/mTOR. Plasmid overexpression of TACC1v25 in Cal27 and Fadu cells; western blotting for pathway markers; CCK-8 proliferation assay; flow cytometry; pharmacological rescue with AKT activator SC79 Cell death discovery Medium 34897285

Source papers

Stage 0 corpus · 20 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon. Oncogene 101 10435627
2003 TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene 79 14603251
2005 Aberrations of TACC1 and TACC3 are associated with ovarian cancer. BMC women's health 67 15918899
2018 FGFR1:TACC1 fusion is a frequent event in molecularly defined extraventricular neurocytoma. Acta neuropathologica 65 29978331
2002 Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators. Oncogene 59 12165861
2008 Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer. Journal of molecular endocrinology 53 18984771
2004 Aurora B -TACC1 protein complex in cytokinesis. Oncogene 43 15064709
2002 Altered splicing pattern of TACC1 mRNA in gastric cancer. Cancer genetics and cytogenetics 42 12547166
2002 Interaction of the transforming acidic coiled-coil 1 (TACC1) protein with ch-TOG and GAS41/NuBI1 suggests multiple TACC1-containing protein complexes in human cells. The Biochemical journal 40 11903063
2021 Neurofibrosarcoma Revisited: An Institutional Case Series of Uterine Sarcomas Harboring Kinase-related Fusions With Report of a Novel FGFR1-TACC1 Fusion. The American journal of surgical pathology 31 33481389
2010 The transforming acidic coiled coil (TACC1) protein modulates the transcriptional activity of the nuclear receptors TR and RAR. BMC molecular biology 20 20078863
2015 Xenopus TACC1 is a microtubule plus-end tracking protein that can regulate microtubule dynamics during embryonic development. Cytoskeleton (Hoboken, N.J.) 11 26012630
2006 Temporal and spatial expression of TACC1 in the mouse and human. Developmental dynamics : an official publication of the American Association of Anatomists 11 16496324
2022 LINC01140 inhibits nonsmall cell lung cancer progression and cisplatin resistance through the miR-4742-5p/TACC1 axis. Journal of biochemical and molecular toxicology 10 35307914
2021 Uterine Sarcoma With FGFR1-TACC1 Gene Fusion: A Case Report and Review of the Literature. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 8 36302190
2022 The novel finding of an FGFR1::TACC1 fusion in an undifferentiated spindle cell sarcoma of soft tissue with aggressive clinical course. Genes, chromosomes & cancer 6 35064610
2021 FGFR1-TACC1 fusion associated with malignant transformation in a primary spinal cord glioma: a case report. Journal of spine surgery (Hong Kong) 5 34734147
2013 Efficient downregulation of ErbB-2 induces TACC1 upregulation in breast cancer cell lines. Oncology reports 4 23354013
2021 Loss of TACC1 variant25 inducing cell proliferation and suppressing autophagy in head and neck squamous carcinoma. Cell death discovery 3 34897285
2021 Leptomeningeal Dissemination of Low-Grade Neuroepithelial Tumor with FGFR1_TACC1 Fusion with Clinical and Radiographic Response to Pazopanib and Topotecan. Pediatric neurosurgery 1 34749374