Affinage

Showing TPCN1 — TPC1 is a alias.

TPCN1

Two pore channel protein 1 · UniProt Q9ULQ1

Length
816 aa
Mass
94.1 kDa
Annotated
2026-06-10
61 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TPCN1 (TPC1) encodes a homodimeric, two-domain (2×6-TM) voltage-gated cation channel that resides in acidic endomembranes — early/recycling endosomes in animal cells and the vacuole in plants — where it converts membrane voltage and lipid/ion cues into local Ca2+ (and Na+) signals (PMID:29562233, PMID:24776928, PMID:28855648, PMID:23845012). Cryo-EM of mouse TPC1 in apo-closed and PtdIns(3,5)P2-bound open states established that a coin-slot selectivity filter sets Na+ selectivity, that only the voltage-sensing domain of the second 6-TM module confers voltage dependence, and that endolysosome-specific PtdIns(3,5)P2 binds the first 6-TM domain to open the channel under depolarization (PMID:29562233); whole-organelle patch clamp confirmed TPC1 as a depolarization-activated, non-inactivating Na+ channel (lysoNaV) gated by luminal pH (PMID:24776928). In reconstituted bilayers human TPC1 is activated by the second messenger NAADP and requires acidic luminal pH and high luminal Ca2+, with voltage tuning NAADP affinity to support Ca2+ oscillations (PMID:22500018). Channel function depends on dimerization through a C-terminal antiparallel coiled-coil (PMID:26781468), and in plant orthologs Ca2+ gating is set by cytosolic EF-hands and a distinct luminal Ca2+ site whose D454N (fou2) mutation removes luminal Ca2+ inhibition (PMID:21736651, PMID:21764990, PMID:19298454). Functionally, TPC1 supplies local Ca2+ for SNARE/syntaxin-mediated vesicle fusion in early/recycling endosomes and is required for endosomal toxin trafficking (PMID:25135478, PMID:28855648). These channel-dependent Ca2+ signals are physiologically consequential: TPC1 controls endolysosomal Ca2+ uptake and ER store filling to regulate mast cell exocytosis and anaphylaxis (PMID:32661165), drives endolysosome-to-ER calcium-induced calcium release that can deplete ER stores and trigger apoptosis (PMID:40709664), supports myoseptal-junction maintenance via endolysosomal trafficking (PMID:35393618) and dynamic proximal-tubular phosphate reabsorption (PMID:36599408), and promotes cancer cell proliferation and progression through NAADP/CICR signaling and mTORC1/TFEB control (PMID:30991693, PMID:39524724). In plants the vacuolar channel additionally propagates systemic Ca2+ waves in concert with NADPH-oxidase-derived ROS (PMID:27261066).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2004 Medium

    Established that TPC1 is specifically required for ROS-evoked Ca2+ entry, distinguishing it from osmotically-driven Ca2+ pathways and giving the channel its first defined physiological stimulus.

    Evidence Aequorin Ca2+ monitoring in tobacco BY-2 cells with TPC1 cosuppression/overexpression and ion pharmacology

    PMID:15464979

    Open questions at the time
    • Did not resolve subcellular site of the Ca2+ flux
    • Channel biophysics and gating not directly measured
  2. 2009 High

    Identified a luminal Ca2+ recognition site, showing the fou2 D454N mutation removes Ca2+-dependent inhibition and links luminal Ca2+ sensing to gating.

    Evidence Patch clamp of Arabidopsis mesophyll vacuoles comparing wild-type and D454N channels under varying luminal Ca2+

    PMID:19298454

    Open questions at the time
    • Mechanism connecting the site to the gate not yet mapped
    • Plant ortholog only
  3. 2011 High

    Resolved how cytosolic and luminal Ca2+ control gating by assigning EF-hand 2 as the essential activating site and defining the luminal Ca2+ pocket residues that couple to the gate.

    Evidence Site-directed mutagenesis of EF-hand and luminal acidic residues with vacuolar patch clamp and molecular modeling

    PMID:21736651 PMID:21764990

    Open questions at the time
    • Established in plant TPC1; animal regulation by luminal Ca2+ addressed separately
    • No structural model at the time
  4. 2012 High

    Demonstrated that human TPC1 is an NAADP-activated channel requiring acidic luminal pH and high luminal Ca2+, providing a biophysical mechanism for NAADP-induced Ca2+ oscillations.

    Evidence Lipid bilayer reconstitution of native and recombinant TPC1 with conductance, voltage, and ligand-affinity measurements

    PMID:22500018

    Open questions at the time
    • NAADP binding shown functionally but accessory binding protein not yet identified
    • Single-lab in vitro system
  5. 2014 High

    Defined TPC1 as a depolarization-activated, non-inactivating endolysosomal Na+ channel (lysoNaV) gated by luminal pH, establishing its native ionic identity in animal organelles.

    Evidence Whole-organelle patch clamp with heterologous expression and luminal pH manipulation

    PMID:24776928

    Open questions at the time
    • Reconciliation of Na+ selectivity with NAADP-evoked Ca2+ signaling left open
    • Downstream effectors not addressed
  6. 2014 High

    Localized TPC1 function to early/recycling endosomal trafficking, distinguishing it from TPC2's lysosomal degradation role using clean knockouts.

    Evidence Tpcn1−/− and Tpcn2−/− MEFs with cholera toxin trafficking, pH, and morphology assays

    PMID:25135478

    Open questions at the time
    • Molecular partners mediating trafficking not yet defined
    • Link between channel activity and trafficking step not established
  7. 2016 High

    Showed C-terminal coiled-coil dimerization is obligatory for channel activity, defining the structural basis of the functional dimer.

    Evidence BiFC, Co-IP, synthetic peptide dimerization, mutagenesis, ion transport assay, and MD simulation

    PMID:26781468

    Open questions at the time
    • How dimerization couples to gating not resolved
    • Plant channel context
  8. 2017 High

    Connected TPC1 channel function to vesicle fusion by identifying syntaxin interactors in native complexes, framing TPC1 as a local Ca2+ source for SNARE-mediated fusion.

    Evidence Native proteomics (MS) of TPC1 complexes plus co-localization and toxin-processing assays in knockout cells

    PMID:28855648

    Open questions at the time
    • Direct Ca2+-to-SNARE causality not demonstrated
    • Which syntaxins are functionally required not dissected
  9. 2018 High

    Provided atomic-resolution mechanism: cryo-EM in closed and PtdIns(3,5)P2-bound open states explained Na+ selectivity, voltage-sensor asymmetry, and lipid-voltage interplay in activation.

    Evidence Cryo-EM of mouse TPC1 in two states with electrophysiology and mutagenesis

    PMID:29562233

    Open questions at the time
    • NAADP-bound conformation not captured
    • Accessory protein interactions not in structure
  10. 2020 High

    Established an in vivo immune role: TPC1 controls endolysosomal Ca2+ uptake and ER store filling to regulate mast cell degranulation and anaphylaxis.

    Evidence TPC1 knockout mice with passive systemic anaphylaxis, ex vivo degranulation, and Ca2+ homeostasis assays

    PMID:32661165

    Open questions at the time
    • Molecular link between channel flux and ER store filling not detailed
    • Cell-type generality unaddressed
  11. 2024 Medium

    Placed endosomal TPC1 upstream of mTORC1 and TFEB signaling to drive melanoma proliferation and invasion, extending its role to growth-control pathways.

    Evidence CRISPR/Cas9 TPC1 knockout in B16-F0 cells with mTORC1, proliferation, invasion, TFEB localization, and pigmentation assays

    PMID:39524724

    Open questions at the time
    • Mechanism linking channel Ca2+ to mTORC1 not resolved
    • Single cell line, single study
  12. 2025 Medium

    Resolved a spatial signaling mechanism: TPC1 forms a Ca2+ microdomain near IP3R1 at lysosome-ER contact sites to drive CICR, ER store depletion, and apoptosis.

    Evidence TPC1 overexpression/KO and IP3R1 proximity Ca2+ imaging in HeLa cells with ER-stress markers and xenografts

    PMID:40709664

    Open questions at the time
    • Tethering machinery for the contact site not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How accessory NAADP-binding proteins selectively confer NAADP sensitivity on TPC1 across cell types, and how the Na+-selective channel generates the Ca2+ signals attributed to it, remain unresolved.
  • JPT2/HN1L requirement is cell-type-specific and only reported in preprint
  • Direct demonstration of TPC1-mediated Ca2+ flux vs Na+ flux at contact sites still lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140299 molecular sensor activity 3 GO:0008289 lipid binding 1
Localization
GO:0005773 vacuole 5 GO:0005764 lysosome 3 GO:0005768 endosome 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
IP3R1JPT2TPCN2

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 Cryo-EM structures of mouse TPC1 (MmTPC1) in apo closed and PtdIns(3,5)P2-bound open states revealed: (1) a coin-slot-shaped ion selectivity filter defining Na+ selectivity; (2) only the voltage-sensing domain from the second 6-TM domain confers voltage dependence; (3) endolysosome-specific PtdIns(3,5)P2 binds to the first 6-TM domain and activates the channel under depolarizing conditions; (4) structural comparison showed interplay between voltage and ligand in channel activation. Cryo-EM structure determination combined with functional electrophysiology and mutagenesis Nature High 29562233
2014 TPC1 forms a depolarization-activated, non-inactivating Na+ channel (lysoNaV) in endolysosomes. Whole-organelle patch clamp showed TPC1 is a 2×6TM voltage-gated Na+ channel that confers electrical excitability to endolysosomes; luminal alkalization shifts voltage dependence toward hyperpolarization, opening the channel. Whole-organelle patch clamp recording; heterologous expression; pharmacological manipulation of luminal pH Nature chemical biology High 24776928
2012 Human TPC1 incorporated into lipid bilayers is activated by NAADP, requires acidic luminal pH and high luminal Ca2+, operates in two coupled conductance states (47 and 200 pS), and is regulated by membrane voltage; hyperpolarization increases NAADP apparent affinity by ~10 nM/mV, providing a mechanism for NAADP-induced Ca2+ oscillations. Lipid bilayer reconstitution of native and recombinant TPC1; electrophysiology; pharmacological manipulation The Journal of biological chemistry High 22500018
2014 TPC1 loss (Tpcn1−/−) in mouse embryonic fibroblasts impairs trafficking of cholera toxin from the plasma membrane to the Golgi apparatus, indicating TPC1 has a specific role in early/recycling endosomal trafficking distinct from TPC2 (which regulates lysosomal degradation of PDGFRβ). Loss of TPC1 or TPC2 did not significantly affect resting endo-lysosomal pH or morphology. Knockout MEFs (Tpcn1−/− and Tpcn2−/−); cholera toxin trafficking assay; endo-lysosomal pH measurements; morphological analysis Molecular and cellular biology High 25135478
2017 TPC1 localizes predominantly to early and recycling endosomes (not lysosomes) and is required for toxin uptake/processing through early endosomes. Proteomic analysis of native TPC1 channel complexes identified direct interaction with a distinct set of syntaxins involved in intracellular vesicle fusion, suggesting TPC1 provides local Ca2+ for SNARE-mediated vesicle fusion. Knockout cell lines; co-localization with subcellular markers; protein toxin processing assays; native proteomics (mass spectrometry) of TPC1 complexes Scientific reports High 28855648
2011 EF-hand 2 of plant TPC1 is the essential Ca2+-receptor site for Ca2+-dependent channel gating (mutation D376A abolishes activation up to 1 mM Ca2+), while EF-hand 1 is a structural low-affinity Ca2+/Mg2+ site that enables channel responses at physiological Ca2+ concentrations. Single mutation D335A in EF-hand 1 reduces sensitivity below 200 µM Ca2+ but preserves gating. Site-directed mutagenesis of EF-hand residues; patch clamp electrophysiology of vacuoles; molecular modeling The Plant journal : for cell and molecular biology High 21736651
2011 A luminal Ca2+ binding site in TPC1 formed by residues Glu-450, Asp-454, Glu-456, and Glu-457 regulates channel gating by luminal Ca2+; Glu-450 and Asp-454 are directly involved in Ca2+ binding, while Glu-456 and Glu-457 connect the binding site to the gate. The fou2 mutation (D454N) eliminates luminal Ca2+ sensitivity. Structure modeling; site-directed mutagenesis of individual glutamate/aspartate residues; patch clamp recordings of loss-of-TPC1-function protoplasts transiently expressing mutant channels The Plant cell High 21764990
2009 The fou2 gain-of-function point mutation D454N in TPC1 specifically eliminates inhibition by luminal Ca2+ (vacuolar Ca2+ at 0.1 mM level normally abolishes K+ flux through wild-type TPC1 but not the D454N mutant), identifying D454 as part of a luminal Ca2+ recognition/inhibitory site. This leads to higher vacuolar Ca2+/K+ ratio in fou2 plants. Patch clamp measurements on Arabidopsis mesophyll vacuoles; comparison of wild-type and fou2 (D454N) mutant channels under varying luminal Ca2+ concentrations The Plant journal : for cell and molecular biology High 19298454
2016 Dimerization of a C-terminal helix (CTH) of TPC1 is essential for channel activity. Bimolecular fluorescence complementation and co-immunoprecipitation demonstrated C-terminus interaction; synthetic CTH peptides dimerize with Kd = 3.9 µM; deletion or point mutations disrupting CTH dimerization abolish cation transport. MD simulations show CTH forms a stable antiparallel coiled-coil. Bimolecular fluorescence complementation; co-immunoprecipitation; synthetic peptide dimerization assay; site-directed mutagenesis; ion transport assay; molecular dynamics simulations Cellular and molecular life sciences : CMLS High 26781468
2020 TPC1 deficiency in mice leads to enhanced passive systemic anaphylaxis and augmented mast cell histamine release and degranulation ex vivo. TPC1 plays an essential role in endolysosomal Ca2+ uptake and filling of ER Ca2+ stores, thereby regulating exocytosis in mast cells. TPC1 knockout mice; in vivo passive systemic anaphylaxis model; ex vivo mast cell degranulation and histamine release assays; Ca2+ homeostasis measurements Proceedings of the National Academy of Sciences of the United States of America High 32661165
2022 In zebrafish, TPC1-decorated endolysosomes generate localized non-propagating Ca2+ transients at myoseptal junctions (MJs). Loss of tpcn1 (morpholino or CRISPR/Cas9) causes slow skeletal muscle cells to detach from or cross myosepta, disrupts endolysosomal trafficking, and results in abnormal distribution of β-dystroglycan. TPC1-decorated endolysosomes associate with MJs in a microtubule-dependent manner. Antisense morpholino knockdown; CRISPR/Cas9 knockout in zebrafish; Ca2+ imaging; live imaging of endolysosomal dynamics; β-dystroglycan localization analysis Journal of cell science High 35393618
2023 TPC1 is expressed subapically in proximal but not distal kidney tubules. TPC1-deficient mice show prolonged and exaggerated PTH-induced phosphate excretion with delayed recovery, and delayed NH4Cl-induced recovery in acid-base transitions, demonstrating TPC1 is required for dynamic adaptation of proximal tubular phosphate reabsorption. Immunohistochemistry with tubular markers; in vivo PTH bolus injection and acid-base challenge experiments in TPC1-deficient vs. wildtype mice; urine phosphate and ammonium measurements Acta physiologica (Oxford, England) Medium 36599408
2014 Simultaneous knockout of TPC1 and TPC2 in mice leads to mature-onset obesity due to impaired lipid availability and β-adrenergic receptor signaling in brown adipose tissue, with reduced phosphorylated hormone-sensitive lipase and β-adrenergic receptor expression, while mitochondrial respiratory chain function and UCP1 expression remain intact. Tpcn1/2 double knockout mice; body composition analysis; respirometry; BAT temperature measurement; Western blotting for HSL, β-adrenergic receptors, UCP1 Endocrinology Medium 25545384
2019 In human metastatic colorectal cancer cells, NAADP-gated TPC1 triggers Ca2+ release from endo-lysosomes that is amplified by ER InsP3 receptors (CICR). Genetic silencing of TPC1 or pharmacological blockade reduces NAADP-evoked Ca2+ release, serum-induced Ca2+ signals, ERK and Akt phosphorylation, and cell proliferation. Liposomal NAADP delivery; Ca2+ imaging; GPN/nigericin lysosomal Ca2+ depletion; NED-19 pharmacology; TPC1 siRNA knockdown; Western blotting for ERK/Akt phosphorylation; proliferation assays Cancers Medium 30991693
2024 TPC1 knockout in murine B16-F0 melanoma cells decreases mTORC1 activity, reduces proliferation and invasiveness, and increases pigmentation associated with nuclear localization of transcription factor TFEB, demonstrating TPC1 in early/recycling endosomes controls melanoma progression via mTORC1 and TFEB signaling. CRISPR/Cas9 TPC1 knockout in B16-F0 cells; mTORC1 activity assays; proliferation and invasion assays; TFEB localization imaging; pigmentation assay Heliyon Medium 39524724
2025 At lysosome-ER membrane contact sites, TPC1 forms a Ca2+ microdomain in close proximity to IP3R1; proximity of TPC1 to IP3R1 generates Ca2+-induced Ca2+ release that depletes ER Ca2+ stores and triggers lethal ER stress-induced apoptosis. Altering TPC1 expression levels in HeLa cells replicates these calcium dynamics. RAB7A activity assays; lysosome-ER proximity imaging; TPC1 overexpression/KO in HeLa cells; Ca2+ imaging; ER stress markers; BALB/c xenograft models Advanced science Medium 40709664
2016 In Arabidopsis roots, TPC1 vacuolar channel participates in propagation of systemic Ca2+ waves in response to salt stress. The Ca2+ wave transmission requires both TPC1-dependent Ca2+ release and AtRBOHD NADPH oxidase-generated extracellular ROS; a ROS-assisted calcium-induced calcium-release (CICR) mechanism explains the observed wave speeds, as shown by ROS scavenger treatment, NADPH oxidase inhibition, and atrbohD knockout experiments. Fire-diffuse-fire modeling; Ca2+ wave imaging; ROS scavenger (ascorbate) and NADPH oxidase inhibitor (DPI) treatment; AtrbohD knockout analysis; extracellular ROS imaging Plant physiology Medium 27261066
2010 Guard cells express higher TPC1 transcript levels and higher SV channel current density than mesophyll cells, and guard cell SV/TPC1 channels have higher cytosolic Ca2+ sensitivity than mesophyll cell channels, explaining the stomatal phenotype of tpc1-2 loss-of-function plants. Quantitative RT-PCR for TPC1 transcripts; patch clamp measurements of SV currents in guard cell and mesophyll vacuoles; comparison of Ca2+ dose-response curves Plant & cell physiology Medium 20630987
2004 TPC1 channels are specifically required for ROS-responsive Ca2+ influx in tobacco cells: cells cosuppressing endogenous TPC1 lose H2O2-induced Ca2+ influx, while AtTPC1 overexpression increases Al-sensitive (TPC1-dependent) Ca2+ influx. Hypoosmotic Ca2+ influx is TPC1-independent. Al ions specifically inhibit TPC1-mediated Ca2+ influx. Aequorin-based Ca2+ monitoring in BY-2 cells; TPC1 overexpression and cosuppression lines; Al, La, Gd ion pharmacology; H2O2 and hypoosmotic stimulation Biochemical and biophysical research communications Medium 15464979
2013 Monocot TPC1 orthologs (OsTPC1 from rice, TaTPC1 from wheat) functionally rescue the SV channel deficit in Arabidopsis tpc1-2 vacuoles, demonstrating conserved vacuolar localization and function. When expressed in HEK293 cells, OsTPC1 targets to LysoTracker-positive organelles, confirming endomembrane localization across phyla. Cross-species complementation of tpc1-2 mutant; patch clamp of vacuoles from Arabidopsis and rice tpc1 null mutants; LysoTracker imaging in HEK293 cells The New phytologist Medium 23845012
2062 JPT2/HN1L functions as an NAADP-binding protein required for NAADP-mediated Ca2+ release via TPC1/TPC2 in a cell-type-specific manner; it is indispensable in CD4+ T cells (TCR/CD3-evoked Ca2+ microdomains reduced in Jpt2/Hn1l−/− cells) but dispensable in cardiomyocytes, platelets, and mast cells. Jpt2/Hn1l−/− mouse generation; NAADP-evoked Ca2+ imaging in primary cardiomyocytes, mast cells, T cells; platelet aggregation assays; TCR/CD3 stimulation bioRxivpreprint Medium bio_10.1101_2025.11.11.687795

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 The vacuolar Ca2+-activated channel TPC1 regulates germination and stomatal movement. Nature 377 15772667
2016 A ROS-Assisted Calcium Wave Dependent on the AtRBOHD NADPH Oxidase and TPC1 Cation Channel Propagates the Systemic Response to Salt Stress. Plant physiology 199 27261066
2018 Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel. Nature 160 29562233
2014 The voltage-gated sodium channel TPC1 confers endolysosomal excitability. Nature chemical biology 148 24776928
2011 TPC1-SV channels gain shape. Molecular plant 122 21459829
2009 The fou2 mutation in the major vacuolar cation channel TPC1 confers tolerance to inhibitory luminal calcium. The Plant journal : for cell and molecular biology 94 19298454
2011 A novel calcium binding site in the slow vacuolar cation channel TPC1 senses luminal calcium levels. The Plant cell 83 21764990
2014 TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2. Molecular and cellular biology 79 25135478
2012 Membrane potential regulates nicotinic acid adenine dinucleotide phosphate (NAADP) dependence of the pH- and Ca2+-sensitive organellar two-pore channel TPC1. The Journal of biological chemistry 69 22500018
2011 Differential contribution of EF-hands to the Ca²⁺-dependent activation in the plant two-pore channel TPC1. The Plant journal : for cell and molecular biology 59 21736651
2018 Structure and Function of TPC1 Vacuole SV Channel Gains Shape. Molecular plant 50 29614320
2017 The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes. Scientific reports 49 28855648
2019 Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Induces Intracellular Ca2+ Release through the Two-Pore Channel TPC1 in Metastatic Colorectal Cancer Cells. Cancers 44 30991693
2017 Tpc1 is an important Zn(II)2Cys6 transcriptional regulator required for polarized growth and virulence in the rice blast fungus. PLoS pathogens 42 28742127
2004 Aluminum as a specific inhibitor of plant TPC1 Ca2+ channels. Biochemical and biophysical research communications 40 15464979
2012 Berberine inhibited the growth of thyroid cancer cell lines 8505C and TPC1. Yonsei medical journal 36 22318822
2019 Effects of curcumin and its adjuvant on TPC1 thyroid cell line. Chemico-biological interactions 34 30935902
2020 TPC1 deficiency or blockade augments systemic anaphylaxis and mast cell activity. Proceedings of the National Academy of Sciences of the United States of America 33 32661165
2018 Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell line. BMC complementary and alternative medicine 32 29448931
2018 Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway. Oncology letters 32 30127885
2010 Guard cell-specific calcium sensitivity of high density and activity SV/TPC1 channels. Plant & cell physiology 32 20630987
1995 Molecular and cytogenetic characterization of a t(1;10;21) translocation in the human papillary thyroid cancer cell line TPC-1 expressing the ret/H4 chimeric transcript. Surgery 31 7491517
2016 5'-AMP-Activated Protein Kinase Regulates Papillary (TPC-1 and BCPAP) Thyroid Cancer Cell Survival, Migration, Invasion, and Epithelial-to-Mesenchymal Transition. Thyroid : official journal of the American Thyroid Association 29 27121619
2013 On the cellular site of two-pore channel TPC1 action in the Poaceae. The New phytologist 26 23845012
2011 Cell-specific compartmentation of mineral nutrients is an essential mechanism for optimal plant productivity--another role for TPC1? Plant signaling & behavior 25 22067997
1996 A novel multicolor hybridization scheme applied to localization of a transcribed sequence (D10S170/H4) and deletion mapping in the thyroid cancer cell line TPC-1. Cytogenetics and cell genetics 25 9067436
2016 The function of the two-pore channel TPC1 depends on dimerization of its carboxy-terminal helix. Cellular and molecular life sciences : CMLS 24 26781468
2015 Normal human thyroid cells, BCPAP, and TPC-1 thyroid tumor cell lines display different profile in both basal and TNF-α-induced CXCL8 secretion. Endocrine 24 26450713
2014 Absence of intracellular ion channels TPC1 and TPC2 leads to mature-onset obesity in male mice, due to impaired lipid availability for thermogenesis in brown adipose tissue. Endocrinology 24 25545384
2015 MicroRNA-145 inhibits human papillary cancer TPC1 cell proliferation by targeting DUSP6. International journal of clinical and experimental medicine 23 26309510
2020 Metformin Inhibits Proliferation of Human Thyroid Cancer TPC-1 Cells by Decreasing LRP2 to Suppress the JNK Pathway. OncoTargets and therapy 22 32021253
2020 Pseudomonas aeruginosa synthesized silver nanoparticles inhibit cell proliferation and induce ROS mediated apoptosis in thyroid cancer cell line (TPC1). Artificial cells, nanomedicine, and biotechnology 20 32432484
2019 Metformin induces TPC-1 cell apoptosis through endoplasmic reticulum stress-associated pathways in vitro and in vivo. International journal of oncology 20 31180536
2019 Long non-coding RNA UCA1 exerts growth modulation by miR-15a in human thyroid cancer TPC-1 cells. Artificial cells, nanomedicine, and biotechnology 19 31062608
2005 Action of aluminum, novel TPC1-type channel inhibitor, against salicylate-induced and cold-shock-induced calcium influx in tobacco BY-2 cells. Biochemical and biophysical research communications 19 15913561
2019 Schizandrin A inhibits proliferation, migration and invasion of thyroid cancer cell line TPC-1 by down regulation of microRNA-429. Cancer biomarkers : section A of Disease markers 17 30909188
2011 Dissection of the RET/β-catenin interaction in the TPC1 thyroid cancer cell line. American journal of cancer research 17 22016822
2023 TPC1 vacuole SV channel gains further shape - voltage priming of calcium-dependent gating. Trends in plant science 16 36740491
2022 Major vacuolar TPC1 channel in stress signaling: what matters, K+, Ca2+ conductance or an ion-flux independent mechanism? Stress biology 16 37676554
2018 Bleomycin inhibits proliferation and induces apoptosis in TPC-1 cells through reversing M2-macrophages polarization. Oncology letters 16 30127999
2016 Adaptive molecular evolution of the two-pore channel 1 gene TPC1 in the karst-adapted genus Primulina (Gesneriaceae). Annals of botany 12 27582362
2012 Alpha-lipoic acid induces sodium iodide symporter expression in TPC-1 thyroid cancer cell line. Nuclear medicine and biology 11 22995901
2021 Effects of Nanosecond Pulsed Electric Fields in Cell Vitality, Apoptosis, and Proliferation of TPC-1 Cells. Analytical cellular pathology (Amsterdam) 10 34692376
2023 Two-pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling. Acta physiologica (Oxford, England) 5 36599408
2019 [The mechanism of aspirin combined with metformin induced apoptosis of thyroid cancer TPC-1 cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 4 31014052
2025 Activation of Lysosomal Retrograde Transport Triggers TPC1-IP3R1 Ca2+ Crosstalk at Lysosome-ER MCSs Leading to Lethal Depleting of ER Calcium. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 3 40709664
2023 Circular RNA eukaryotic translation initiation factor 6 facilitates TPC-1 cell proliferation and invasion through the microRNA-138-5p/lipase H axis. Functional & integrative genomics 3 37776372
2022 Localized TPC1-mediated Ca2+ release from endolysosomes contributes to myoseptal junction development in zebrafish. Journal of cell science 3 35393618
2021 Cep63 knockout inhibits the malignant phenotypes of papillary thyroid cancer cell line TPC‑1. Oncology reports 3 34296302
2003 A generalized transducing thiophage (TPC-1) of a facultative sulfur chemolithotrophic bacterium, Bosea thiooxidans CT5, of alpha-Proteobacteria, isolated from Indian soil. FEMS microbiology letters 3 14568152
2025 Therapeutic Potential of CAPE in Targeting Hallmarks of Cancer in TPC-1 Thyroid Cancer Cells Through Modulation of Mitochondrial Membrane Potential. Journal of biochemical and molecular toxicology 2 40901741
2024 Vernodalin Triggers ROS-Mediated Apoptosis in TPC-1 Human PapillaryThyroid Cancer Cells via Suppression of the MAPKs Signaling Pathway. Combinatorial chemistry & high throughput screening 1 39099452
2021 [Knockdown of long non-coding RNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) inhibits epithelial-mesenchymal transition, invasion and migration of TPC-1 papillary thyroid cancer cells]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 1 33441229
2019 [Expression of Lysosomal Membrane Proteins LAMP1, TPC1 and TPC2 in Acute Myeloid Leukemia Cells and Its Clinical Significance]. Zhongguo shi yan xue ye xue za zhi 1 31418355
2026 Effects of miR-451 on the proliferation, invasion and migration of papillary thyroid cancer cell line TPC-1 by regulating the PI3K/AKT/mTOR signaling pathway. Endocrine connections 0 41705518
2025 ANTP-SmacN7 enhances radiosensitivity in TPC-1 cells through XIAP-mediated activation of apoptotic protein. Scientific reports 0 40670515
2024 CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway. Open medicine (Warsaw, Poland) 0 38868316
2024 TPC1 regulates melanoma tumourigenesis via mTORC1 and TFEB. Heliyon 0 39524724
2023 Antineoplastic properties of polyphenols in TPC-1 human papillary thyroid carcinoma cell line: a systematic review. Archives of endocrinology and metabolism 0 37364147
2022 Influence of Dehydroxymethylepoxyquinomicin on Radiosensitivity of Thyroid Carcinoma TPC-1 Cells. Journal of oncology 0 36213820
2021 [Study on Cep63 expression and apoptosis of thyroid papillary carcinoma cell lines TPC-1]. Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 0 33472304

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