Affinage

TNKS

Poly [ADP-ribose] polymerase tankyrase-1 · UniProt O95271

Round 2 corrected
Length
1327 aa
Mass
142.0 kDa
Annotated
2026-04-28
63 papers in source corpus 24 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TNKS (tankyrase-1) is a poly(ADP-ribose) polymerase that PARsylates diverse substrates to couple ADP-ribosylation with RNF146-mediated ubiquitination and proteasomal degradation, thereby controlling telomere maintenance, Wnt/β-catenin signaling, mitotic progression, insulin-stimulated GLUT4 trafficking, peroxisome import, and necroptosis. At telomeres, TNKS PARsylates TRF1, releasing it from telomeric DNA and licensing its ubiquitin-dependent degradation, which permits telomerase-dependent telomere elongation; during mitosis, TNKS is required for resolution of sister-telomere cohesion (PMID:9822378, PMID:12782650, PMID:15064417). In the Wnt pathway, TNKS PARsylates axin, promoting its RNF146-dependent ubiquitination and degradation to relieve β-catenin destruction-complex activity; TNKS additionally exerts a scaffolding function within this complex that is mechanistically separable from its catalytic role (PMID:19759537, PMID:21478859, PMID:25327252). Cherubism-causing mutations in 3BP2 abolish the TNKS-binding motif required for tankyrase-mediated 3BP2 destruction, establishing a direct genetic link between escape from TNKS-dependent PARdU and this Mendelian bone disorder (PMID:22153076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    The discovery that tankyrase is a telomere-associated PARP that ADP-ribosylates TRF1, reducing its DNA-binding capacity, established TNKS as the first enzyme directly linking ADP-ribosylation to telomere-length regulation.

    Evidence Yeast two-hybrid, Co-IP, and in vitro PARP assay with recombinant tankyrase and TRF1

    PMID:9822378

    Open questions at the time
    • Identity of the E3 ligase mediating TRF1 degradation was unknown
    • In vivo telomere elongation requirement for TNKS catalytic activity was not tested
    • Endogenous regulation of TNKS PARP activity remained undefined
  2. 2000 High

    Demonstrating that tankyrase localizes to Golgi/GLUT4 vesicles, binds IRAP via its ankyrin repeats, and is activated by MAPK-dependent phosphorylation expanded its functional scope beyond telomeres to insulin-responsive vesicle trafficking.

    Evidence Subcellular fractionation, immunofluorescence, IRAP peptide-binding assay, and in vitro MAPK phosphorylation/PARP activity assay in adipocytes

    PMID:10988299

    Open questions at the time
    • Whether TNKS PARP activity toward IRAP has a functional consequence on GLUT4 translocation was not tested
    • The downstream signaling cascade linking TNKS to glucose uptake was uncharacterized
  3. 2002 High

    Establishing that both TNKS1 and TNKS2 are bona fide PARPs capable of releasing TRF1 from telomeres, and that telomere elongation requires both TNKS catalytic activity and telomerase, placed tankyrase-mediated PARsylation upstream of telomerase access in the telomere-lengthening pathway.

    Evidence In vitro PARP assay with catalytic mutants, nuclear overexpression, and telomere length analysis

    PMID:11739745

    Open questions at the time
    • Relative contributions of TNKS1 versus TNKS2 at telomeres were unclear
    • Whether TNKS functions redundantly or cooperatively with TNKS2 in vivo was untested
  4. 2003 High

    Discovery that TRF1 ADP-ribosylation by tankyrase leads to sequential ubiquitination and proteasomal degradation of TRF1 — and separately that tankyrase 1 knockdown causes mitotic arrest through persistent sister-telomere cohesion — defined two distinct cell-cycle functions: licensing telomerase access in S phase and resolving telomeric cohesion for anaphase.

    Evidence Ubiquitination assays with proteasome inhibitors, immunofluorescence of TRF1 release; RNAi of TNKS1 with mitotic chromosome analysis

    PMID:12768206 PMID:12782650 PMID:15064417

    Open questions at the time
    • The E3 ubiquitin ligase targeting PARsylated TRF1 was still unknown
    • Mechanism by which TNKS resolves telomeric cohesion (PARsylation of cohesion factors?) was unidentified
  5. 2009 High

    Identification of tankyrase as the direct target of the Wnt pathway inhibitor XAV939 — and demonstration that TNKS PARsylates axin to promote its ubiquitin-dependent degradation — fundamentally recast tankyrase as a central Wnt signaling regulator beyond its telomeric role.

    Evidence Chemical genetic screen, quantitative chemical proteomics, PARP inhibition assay, axin stability and Wnt reporter assays

    PMID:19759537

    Open questions at the time
    • The E3 ligase coupling axin PARsylation to ubiquitination was not identified
    • Whether TNKS scaffolding contributes independently of catalysis was unknown
  6. 2011 High

    Identification of RNF146 as the PAR-directed E3 ligase that recognizes tankyrase-generated poly(ADP-ribose) via its WWE domain, ubiquitinating both axin and tankyrase itself, unified the PARsylation-dependent ubiquitination (PARdU) mechanism and extended it to the disease substrate 3BP2, whose escape from this pathway causes cherubism.

    Evidence Proteomics/RNAi screens, in vitro WWE–PAR binding, ubiquitination assays, Wnt reporters, mouse cherubism model with 3BP2 TBM mutations

    PMID:21478859 PMID:21799911 PMID:22153076

    Open questions at the time
    • Full substrate repertoire of the TNKS–RNF146 PARdU axis was incomplete
    • Structural basis of allosteric RNF146 activation by PAR was unresolved
  7. 2012 High

    Demonstration that axin, TNKS2, and KIF3A form an insulin-regulated ternary complex required for GLUT4 translocation — and that TNKS2 knockout mice exhibit impaired insulin sensitivity — placed tankyrase within an Akt-dependent insulin-signaling pathway controlling glucose homeostasis.

    Evidence Co-IP, TNKS2 knockout mice with metabolic phenotyping, GLUT4 translocation and ADP-ribosylation assays, Akt inhibitor experiments

    PMID:22473005

    Open questions at the time
    • Whether TNKS1 compensates for TNKS2 in GLUT4 regulation was not addressed
    • The precise PARsylation substrate(s) mediating vesicle transport were not defined
  8. 2014 High

    Crystal structures of the RNF146–tankyrase complex revealed that iso-ADP-ribose binding allosterically activates RNF146 and that PARdU occurs within a preformed TNKS–RNF146 complex, providing the structural basis of coupled PARsylation-ubiquitination.

    Evidence X-ray crystallography, mutagenesis, cell-based axin turnover assay

    PMID:25327252

    Open questions at the time
    • How substrate specificity is determined within the TNKS–RNF146 complex was unclear
    • Whether other PAR-binding E3 ligases substitute for RNF146 on specific substrates was unknown
  9. 2022 Medium

    Discovery that USP25 deubiquitinates TNKS1 to stabilize it, and that disrupting the TNKS–USP25 interaction pharmacologically (UAT-B) promotes TNKS degradation and suppresses Wnt signaling, identified a druggable regulatory axis controlling tankyrase protein levels independently of catalytic inhibition.

    Evidence Co-IP, ubiquitination assays, USP25 knockdown/overexpression in glioma cells; PPI inhibitor UAT-B with in vivo CRC xenograft models

    PMID:35450028 PMID:38261825

    Open questions at the time
    • USP25–TNKS interaction validated in limited cell types
    • Whether USP25 regulates TNKS2 equally is untested
    • Structural basis of the TNKS–USP25 interface is unknown
  10. 2024 High

    Two studies expanded TNKS substrates and contexts: TNKS binds PEX14 at peroxisomes to regulate peroxisome import via PARsylation, linking peroxisome loss to enhanced axin degradation and Wnt activation; separately, TNKS and RNF146 form phase-separated condensates (recruited by TAX1BP1) that PARsylate and ubiquitinate RIPK1-K376 to restrain necroptosis.

    Evidence Genome-wide CRISPRi screen with peroxisome import assays; in vitro phase-separation/PARdU reconstitution with K376 mutagenesis and MEF necroptosis model

    PMID:38272024 PMID:38967608

    Open questions at the time
    • Full set of peroxisomal TNKS PARsylation substrates unknown
    • Whether TNKS condensate formation occurs in vivo during necroptosis awaits confirmation
    • Quantitative contribution of TNKS-RIPK1 axis relative to other RIPK1 regulatory mechanisms is unclear
  11. 2025 Medium

    Comparison of TNKS catalytic inhibitors versus chemically induced TNKS degraders revealed that TNKS possesses a scaffolding function within the β-catenin destruction complex — inhibitor-stabilized TNKS induces axin puncta and rigidifies the complex, paradoxically impeding β-catenin turnover — establishing that removing TNKS protein provides deeper Wnt suppression than catalytic inhibition alone.

    Evidence (Preprint) TNKS degrader vs. inhibitor imaging, β-catenin turnover assay, CRC organoid proliferation

    Open questions at the time
    • Preprint not yet peer-reviewed
    • Structural basis of TNKS scaffolding within the destruction complex is undefined
    • In vivo therapeutic window for TNKS degraders versus inhibitors not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the full substrate repertoire of the TNKS–RNF146 PARdU axis, the structural determinants of substrate selectivity within the tankyrase ankyrin-repeat cage, the physiological relevance of TNKS phase separation beyond necroptosis, and whether TNKS1 and TNKS2 are functionally redundant or have pathway-specific roles in vivo.
  • No comprehensive in vivo substrate catalog exists
  • TNKS1/TNKS2 double-knockout phenotype in adult tissues is incompletely characterized
  • Whether PAR chain length determines substrate fate (degradation vs. signaling) is unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 9 GO:0016740 transferase activity 3
Localization
GO:0005694 chromosome 3 GO:0005794 Golgi apparatus 2 GO:0005815 microtubule organizing center 2 GO:0005634 nucleus 1 GO:0005777 peroxisome 1 GO:0005829 cytosol 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-392499 Metabolism of proteins 6 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 1 R-HSA-5357801 Programmed Cell Death 1
Partners
3BP2AXIN1IRAPPEX14RIPK1RNF146TRF1USP25
Complex memberships
Shelterin-associated TRF1 complexTNKS–RNF146 PARdU complexβ-catenin destruction complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Tankyrase (TNKS) was identified as a poly(ADP-ribose) polymerase (PARP) that localizes to human telomeres and binds TRF1, a negative regulator of telomere length. Recombinant tankyrase showed PARP activity in vitro, ADP-ribosylating both TRF1 and itself; ADP-ribosylation of TRF1 diminished its ability to bind telomeric DNA. In vitro PARP assay, immunofluorescence, yeast two-hybrid/Co-IP for TRF1 interaction Science High 9822378
1999 Tankyrase localizes in a cell-cycle-dependent manner: during interphase it co-localizes with TRF1 at telomeres and also at nuclear pore complexes; at mitosis, it relocates to pericentriolar matrix of centrosomes. Telomeric localization of exogenous tankyrase required co-expression with TRF1. Indirect immunofluorescence, subcellular fractionation, immunoelectron microscopy, co-transfection experiments Journal of cell science High 10523501
2000 Tankyrase is a peripheral membrane protein associated with the Golgi and co-localizes with GLUT4 storage vesicles in adipocytes. Tankyrase binds specifically to IRAP (insulin-responsive aminopeptidase) via its ankyrin repeats interacting with the IRAP cytosolic sequence RQSPDG. Tankyrase is a novel MAPK substrate; insulin stimulation leads to its stoichiometric phosphorylation, which enhances its PARP activity. Subcellular fractionation, immunofluorescence, binding assay (ankyrin repeat domain with IRAP peptide), in vitro PARP assay, MAPK phosphorylation assay The Journal of biological chemistry High 10988299
2002 Tankyrase 2 (TNKS2) is a bona fide PARP that poly(ADP-ribosyl)ates itself and TRF1 in vitro. Overexpression of TNKS2 in the nucleus releases endogenous TRF1 from telomeres, establishing a telomeric role for TNKS2 parallel to TNKS1. Tankyrase 1-mediated telomere elongation requires PARP catalytic activity and depends on telomerase. In vitro PARP assay, nuclear overexpression with immunofluorescence readout, telomere length analysis Molecular and cellular biology High 11739745
2003 ADP-ribosylation of TRF1 by tankyrase 1 releases TRF1 from telomeres, after which TRF1 is ubiquitinated and degraded by the proteasome. Only telomere-unbound TRF1 is ubiquitinated, establishing a sequential post-translational modification mechanism (ADP-ribosylation then ubiquitination) governing telomerase access. Cell-based assays, ubiquitination assays, proteasome inhibitor experiments, immunofluorescence Genes & development High 12782650
2003 TRF1 complex interacts with POT1 (protection of telomeres 1), a single-stranded telomeric DNA-binding protein, transmitting telomere-length information to the terminus where telomerase is regulated; tankyrase 1 is established as part of the TRF1 complex mediating this control. Co-immunoprecipitation, dominant-negative POT1 overexpression, telomere length analysis Nature High 12768206
2003 FBP17 (formin-binding protein 17) binds tankyrase via a specific TNKS-binding motif (TBM), as demonstrated by yeast two-hybrid and co-immunoprecipitation of endogenous proteins in 293T cells. Yeast two-hybrid, co-immunoprecipitation of endogenous proteins FEBS letters Medium 14596906
2004 Knockdown of tankyrase 1 caused mitotic arrest: chromosomes aligned normally but sister chromatids could not segregate, remaining associated at telomeres through proteinaceous bridges, while centromere and arm cohesion was resolved. This established a tankyrase 1-dependent pathway specifically required for sister telomere resolution before anaphase. RNAi knockdown, immunofluorescence, mitotic analysis Science High 15064417
2006 The HIF asparaginyl hydroxylase FIH hydroxylates specific asparagine residues within ankyrin repeat domains (ARDs) of multiple proteins; tankyrase's ankyrin repeat domain is implicated as a potential substrate within this broad ARD hydroxylation mechanism. In vitro hydroxylation assay, mass spectrometry identification of hydroxylation sites PNAS Low 17003112
2009 A chemical genetic screen identified XAV939, which inhibits beta-catenin-mediated transcription by stabilizing axin. Quantitative chemical proteomics revealed that XAV939 acts by inhibiting tankyrase 1 and tankyrase 2. Both tankyrase isoforms interact with a conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway. Chemical genetic screen, quantitative chemical proteomics, biochemical PARP inhibition assay, axin stability assay, ubiquitin-proteasome pathway experiments Nature High 19759537
2011 RNF146, a RING-domain E3 ubiquitin ligase, directly interacts with poly(ADP-ribose) through its WWE domain and promotes degradation of PARsylated proteins including axin. RNF146 acts downstream of tankyrase-dependent PARsylation to couple axin PARsylation to ubiquitylation and proteasomal degradation; BLZF1 and CASC3 were identified as further substrates targeted by tankyrase and RNF146. Proteomics, RNAi screen, Co-IP, in vitro binding assay (WWE domain + PAR), ubiquitination assay, Wnt reporter assay Nature cell biology High 21478859
2011 RNF146 forms a protein complex with tankyrase and axin; RNF146 mediates ubiquitylation of TNKS1, TNKS2, and axin for proteasomal degradation. Tankyrase auto-PARsylation and PARsylation of axin leads to RNF146-mediated ubiquitination and degradation. RNF146 also prevents tankyrase protein aggregation at centrosomes. RNAi screen, Co-IP, ubiquitination assay, Wnt reporter assay, immunofluorescence PloS one High 21799911
2011 Tankyrase regulates the adaptor protein 3BP2 stability through ADP-ribosylation followed by RNF146-mediated ubiquitylation in osteoclasts. Cherubism mutations in 3BP2 (within RSPPDG sequence) uncouple 3BP2 from tankyrase-mediated destruction, causing its stabilization and hyperactivation of SRC, SYK, and VAV signaling pathways. Mouse model, Co-IP, in vitro ADP-ribosylation assay, ubiquitination assay, signaling pathway analysis Cell High 22153076
2011 PARP3 stabilizes the mitotic spindle and regulates tankyrase 1, associating with it as part of mitotic spindle regulation. Loss-of-function models, immunofluorescence, Co-IP PNAS Medium 21270334
2012 Axin forms a ternary complex with tankyrase 2 (TNKS2) and the kinesin motor KIF3A that is required for insulin-stimulated GLUT4 translocation to the plasma membrane. Insulin treatment suppresses TNKS ADP-ribosylase activity, reducing ADP-ribosylation and ubiquitination of Axin and TNKS and stabilizing the complex. Akt inhibition abrogates this complex stabilization. TNKS2-knockout mice show reduced insulin sensitivity and elevated blood glucose. Co-IP, knockdown of individual components, TNKS2 knockout mice, GLUT4 translocation assay, ADP-ribosylation assay, Akt inhibitor Cell research High 22473005
2014 RNF146 directly interacts with tankyrase (TNKS) and disruption of the RNF146-TNKS interaction inhibits turnover of axin in cells, indicating that both PARylation of substrate (by TNKS) and PARdU (by RNF146) occur within the same protein complex. Iso-ADP-ribose binds between the WWE and RING domains of RNF146 causing allosteric activation. Structural biology (crystallography), in vitro binding, cell-based axin turnover assay, mutagenesis Nature High 25327252
2014 Family-wide PARP activity analysis confirmed that tankyrase 1 and tankyrase 2 generate poly(ADP-ribose) (PAR), placing them among the minority of PARP family members capable of PAR synthesis (most generate only mono-ADP-ribose). In vitro PARP activity assay with purified recombinant proteins, mass spectrometry identification of modification type Nature communications High 25043379
2020 TNKS-2 poly(ADP-ribosyl)ates VEGF in the Golgi as part of a two-step process: PARP-16 in the ER catalyzes priming mono-ADP-ribosylation of VEGF, which is a prerequisite for subsequent poly-ADP-ribosylation of VEGF by TNKS-2 in the Golgi, reducing VEGF biological activity. Co-immunoprecipitation, in vitro ADP-ribosylation assay, VEGF activity assay Molecular and cellular biochemistry Medium 32472322
2022 USP25 deubiquitinates TNKS1, negatively regulating its ubiquitination level; USP25 overexpression stabilizes TNKS1 and activates Wnt/β-catenin signaling, while USP25 knockdown increases TNKS1 ubiquitination and reduces pathway activity in glioma cells. Co-immunoprecipitation, ubiquitination assay, Western blot, knockdown/overexpression Disease markers Medium 35450028
2023 UAT-B, a neoantimycin analog, inhibits the TNKS-USP25 protein-protein interaction, leading to decreased TNKS levels and activation of Wnt/β-catenin pathway suppression; disruption of the TNKS-USP25 complex (rather than inhibiting TNKS enzymatic activity) is sufficient to promote TNKS degradation and block CRC growth. PPI inhibition assay, Western blot, in vitro and in vivo tumor models, patient-derived xenografts Acta pharmaceutica Sinica. B Medium 38261825
2024 TNKS and TNKS2 bind the peroxisomal membrane protein PEX14 and promote PARsylation of proteins at the peroxisome membrane, where RNF146 regulates peroxisome import efficiency. Loss of peroxisomes increases TNKS/2 and RNF146-dependent degradation of AXIN1, sufficient to alter β-catenin transcriptional amplitude. Genome-wide CRISPRi screen, peroxisome import assay, Co-IP, Western blot, reporter assay The Journal of cell biology High 38967608
2024 Upon induction of necroptosis, PARP5A (TNKS) and RNF146 form liquid-like condensates by multivalent interactions (recruited by TAX1BP1) and perform PARylation and PARylation-dependent ubiquitination (PARdU) of kinase-activated RIPK1, predominantly on K376, promoting its proteasomal degradation and restraining necroptosis. Phase separation assay, Co-IP, in vitro PARylation and ubiquitination assay, site-directed mutagenesis (K376), mouse embryonic fibroblast necroptosis model Molecular cell High 38272024
2025 Catalytic inhibition of TNKS prevents TNKS turnover, causing TNKS accumulation in the β-catenin destruction complex (DC), where TNKS scaffolding function induces AXIN puncta formation, rigidifies the DC, and impedes β-catenin turnover. Chemically induced degradation of TNKS (rather than catalytic inhibition) avoids puncta formation, stabilizes AXIN without this barrier, and provides deeper WNT pathway suppression. Chemical TNKS degrader vs. inhibitor comparison, AXIN puncta imaging, β-catenin turnover assay, colorectal cancer organoid/cell proliferation assay bioRxivpreprint Medium
2025 In skeletal muscle cells, an Akt-Axin1/TNKS-Tiam1-Rac1 signaling axis mediates insulin-stimulated GLUT4 translocation. Insulin up-regulates Axin1 and TNKS protein levels in an Akt-dependent manner; Axin1 interacts with TNKS (interaction enhanced by insulin); TNKS enzymatic inhibition (XAV939) or Axin1 overexpression enhances GLUT4 translocation via Tiam1 upregulation and Rac1-PAK signaling, independently of Akt-AS160. Knockdown and overexpression, Co-IP, GLUT4myc translocation assay, PAK phosphorylation assay, XAV939 treatment in C2C12 myotubes Cellular signalling Medium 41207648
2025 TNKS1 directly interacts with SLC7A11 (xCT) as shown by Co-IP; TNKS1 upregulation triggers ferroptosis in human aortic smooth muscle cells (elevated iron, ROS, lipid peroxidation), driving phenotypic switching from contractile to synthetic phenotype, contributing to aortic dissection pathogenesis. Co-IP (TNKS1–SLC7A11 interaction), Western blot, immunofluorescence, ferroptosis marker assays, scratch-wound assay, in vivo aortic dissection model International immunopharmacology Low 40359887

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 1738 19759537
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1998 Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science (New York, N.Y.) 878 9822378
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 POT1 as a terminal transducer of TRF1 telomere length control. Nature 550 12768206
2014 Family-wide analysis of poly(ADP-ribose) polymerase activity. Nature communications 414 25043379
2011 RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin degradation and Wnt signalling. Nature cell biology 371 21478859
2006 Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia. Molecular psychiatry 345 17043677
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2002 Role for the related poly(ADP-Ribose) polymerases tankyrase 1 and 2 at human telomeres. Molecular and cellular biology 252 11739745
2006 Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). Proceedings of the National Academy of Sciences of the United States of America 244 17003112
2000 Tankyrase is a golgi-associated mitogen-activated protein kinase substrate that interacts with IRAP in GLUT4 vesicles. The Journal of biological chemistry 241 10988299
2010 Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and german study groups. PLoS genetics 237 20421936
2011 Poly(ADP-ribose) polymerase 3 (PARP3), a newcomer in cellular response to DNA damage and mitotic progression. Proceedings of the National Academy of Sciences of the United States of America 231 21270334
2004 Resolution of sister telomere association is required for progression through mitosis. Science (New York, N.Y.) 226 15064417
2015 A deep proteomics perspective on CRM1-mediated nuclear export and nucleocytoplasmic partitioning. eLife 198 26673895
2014 Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal. Nature 197 25327252
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2001 TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. The Journal of biological chemistry 191 11454873
2003 TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres. Genes & development 185 12782650
2011 Ubiquitin ligase RNF146 regulates tankyrase and Axin to promote Wnt signaling. PloS one 183 21799911
1999 Cell cycle dependent localization of the telomeric PARP, tankyrase, to nuclear pore complexes and centrosomes. Journal of cell science 174 10523501
2011 Loss of Tankyrase-mediated destruction of 3BP2 is the underlying pathogenic mechanism of cherubism. Cell 161 22153076
2012 The Axin/TNKS complex interacts with KIF3A and is required for insulin-stimulated GLUT4 translocation. Cell research 70 22473005
2020 circ5615 functions as a ceRNA to promote colorectal cancer progression by upregulating TNKS. Cell death & disease 60 32393760
2019 The tin1 gene retains the function of promoting tillering in maize. Nature communications 50 31811145
2000 Upregulation of telomerase activity by X-irradiation in mouse leukaemia cells is independent of Tert, Terc, Tnks and Myc transcription. Carcinogenesis 29 10753188
2024 PARP5A and RNF146 phase separation restrains RIPK1-dependent necroptosis. Molecular cell 19 38272024
2011 Expression of TNKS1 is correlated with pathologic grade and Wnt/β-catenin pathway in human astrocytomas. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 18 22154485
2023 Pyridine-Based 1,2,4-Triazolo-Tethered Indole Conjugates Potentially Affecting TNKS and PI3K in Colorectal Cancer. ACS medicinal chemistry letters 17 36923920
2021 Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer. Oncology letters 16 34457043
2014 Molecular insights on TNKS1/TNKS2 and inhibitor-IWR1 interactions. Molecular bioSystems 16 24291818
2003 The formin-binding protein 17, FBP17, binds via a TNKS binding motif to tankyrase, a protein involved in telomere maintenance. FEBS letters 16 14596906
2022 Rational design, synthesis and biological evaluation of dual PARP-1/2 and TNKS1/2 inhibitors for cancer therapy. European journal of medicinal chemistry 15 35504210
2019 MEK Inhibition Induces Canonical WNT Signaling through YAP in KRAS Mutated HCT-15 Cells, and a Cancer Preventive FOXO3/FOXM1 Ratio in Combination with TNKS Inhibition. Cancers 13 30717152
2023 A novel TNKS/USP25 inhibitor blocks the Wnt pathway to overcome multi-drug resistance in TNKS-overexpressing colorectal cancer. Acta pharmaceutica Sinica. B 8 38261825
2022 TNKS inhibitors potentiate proliferative inhibition of BET inhibitors via reducing β-Catenin in colorectal cancer cells. American journal of cancer research 7 35411247
2019 Biological Functions of TNKS1 and Its Relationship with Wnt/β-Catenin Pathway in Astrocytoma. OncoTargets and therapy 7 31849489
2017 Discovery of new dual binding TNKS inhibitors of Wnt signaling inhibition by pharmacophore modeling, molecular docking and bioassay. Molecular bioSystems 6 27995250
2011 Pinworm and TNKS inhibitors, an eccentric duo to derail the oncogenic WNT pathway. Clinics and research in hepatology and gastroenterology 6 21782548
2024 A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2. The Journal of cell biology 5 38967608
2022 Deubiquitination of TNKS1 Regulates Wnt/β-Catenin to Affect the Expression of USP25 to Promote the Progression of Glioma. Disease markers 5 35450028
2018 In silico studies on potential TNKS inhibitors: a combination of pharmacophore and 3D-QSAR modelling, virtual screening, molecular docking and molecular dynamics. Journal of biomolecular structure & dynamics 5 30261821
2025 The upregulation of TNKS1 drives the phenotypic switching of vascular smooth muscle cells in aortic dissection through the activation of ferroptosis. International immunopharmacology 3 40359887
2020 Regulation of poly ADP-ribosylation of VEGF by an interplay between PARP-16 and TNKS-2. Molecular and cellular biochemistry 3 32472322
2017 Overexpression of the endoplasmic reticulum stress-inducible gene TIN1 causes abnormal pollen surface morphology in Arabidopsis. Plant biotechnology (Tokyo, Japan) 3 31275024
2023 Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers. Ecotoxicology and environmental safety 2 36603485
1993 T(In1;5)44H, a complex mouse chromosomal rearrangement with a phenotypic effect. Cytogenetics and cell genetics 2 8449042
2025 CREB Regulates Cisplatin Resistance by Targeting TNKS and KDM6A in NSCLC cell-Derived Tumor Spheroid. International journal of biological sciences 1 40860181
2025 The endoplasmic reticulum-associated degradation machinery selectively degrades stress-induced TIN1 during stress recovery. Plant physiology 1 41052900
2026 TNKS1 mediates the PTEN-PI3K/AKT pathway to regulate glycolysis and proliferation in gliomas. IBRO neuroscience reports 0 41660562
2025 Selective Dual Inhibition of TNKS1 and CDK8 by TCS9725 Attenuates STAT1/β-Catenin/TGFβ1 Signaling in Renal Cancer. Current issues in molecular biology 0 40699862
2025 Targeted inhibition of human Tankyrase-1 (TNKS1) by ZT-5483 exhibited anti-parasitic activity in Toxoplasma gondii: An in silico-based, high-throughput virtual screen and in vitro approach. Molecular and biochemical parasitology 0 41109662
2025 Akt-Axin1/TNKS-Tiam1-Rac1 mediates insulin-stimulated GLUT4 translocation in skeletal muscle cells. Cellular signalling 0 41207648
2022 Combinatorial Virtual Screening Revealed a Novel Scaffold for TNKS Inhibition to Combat Colorectal Cancer. Biomedicines 0 35052822
2021 Erratum: Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer. Oncology letters 0 34966450