Tnks 2 Antibody (C-term)
- Known as:
- Tnks 2 Antibody (C-terminus)
- Catalog number:
- AP5313b-ev20
- Category:
- -
- Supplier:
- Abgen
- Gene target:
- Tnks 2 Antibody (C-term)
Related genes to: Tnks 2 Antibody (C-term)
- Gene:
- TNKS NIH gene
- Name:
- tankyrase
- Previous symbol:
- -
- Synonyms:
- TIN1, TINF1, TNKS1, PARP-5a, PARP5A, pART5
- Chromosome:
- 8p23.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-08
- Date modifiied:
- 2016-03-01
Related products to: Tnks 2 Antibody (C-term)
Related articles to: Tnks 2 Antibody (C-term)
- Tankyrases (TNKS1/2) are multi-domain poly(ADP-ribose) polymerases that regulate Wnt/β-catenin signaling and broader cellular programs through both catalytic activity and extensive protein-protein interaction (PPI) networks. While most tankyrase-directed drug discovery has focused on inhibiting the PARP catalytic site, an emerging alternative is to target tankyrase stability by disrupting its interaction with the deubiquitinase USP25. USP25 functions as a positive regulator of tankyrase abundance by counteracting ubiquitin-dependent turnover; consequently, blocking the TNKS-USP25 PPI can reduce tankyrase levels, stabilize pathway antagonists such as AXIN, and dampen Wnt transcriptional output. In this review, we discuss current understanding of tankyrase domain architecture with emphasis on ankyrin repeat clusters (ARC1/2/4/5) that recognize short tankyrase-binding motifs (TBMs), and we highlight why ARC5 is a particularly actionable node for intervention in the TNKS-USP25 axis. We summarize the structural basis of USP25 recruitment a C-terminal TBM-like element, discuss ARC hotspot features that support ligandability, and provide a practical chemical-biology framework for validating PPI disruption using orthogonal assays (co-immunoprecipitation/proximity ligation, biophysics such as SPR/ITC, cellular target engagement, and displacement formats including FP/FRET). We then evaluate reported small-molecule disruptors, including C44 and UAT-B, as proof-of-concept agents that link ARC5-centered binding to tankyrase destabilization and antitumor phenotypes in prostate cancer and multidrug-resistant colorectal cancer models. Finally, we outline key challenges-selectivity across ARCs, off-target risk, and context-dependent biology-and propose future directions, including structure-guided optimization, improved cell-active chemotypes, and dual-mechanism strategies that combine PPI disruption with catalytic inhibition or targeted degradation approaches. - Source: PubMed
Publication date: 2026/07/06
Kamel Emadeldin MKhadrawy Sally MostafaAli Mohamed A MAhmed Noha AAlkhedhairi SalehAba Alkhayl Faris FLamsabhi Al Mokhtar - Chemotherapy remains the most preferred therapeutic option for Triple-Negative breast cancer (TNBC), but patients frequently develop resistance over time, which remains a major clinical challenge, leading to poor patient treatment outcomes. - Source: PubMed
Publication date: 2026/07/09
Jan ShariqaFatima KaneezKhan Sameer UllahMalik Fayaz A - Amyotrophic Lateral Sclerosis (ALS) is a rare and fatal neurodegenerative disease characterized by the hallmark cytoplasmic accumulation and aggregation of TAR DNA binding protein 43 (TDP-43), which impairs proteasome activity through its interaction with Tankyrase (TNKS). Using molecular and imaging techniques, we have identified a novel role for the Fragile X Mental Retardation Protein (FMRP) in regulating the TNKS/PI31-mediated proteasome activation mechanism in co-operation with TDP-43. Our results demonstrate that depletion of FMRP causes nuclear translocation of TDP-43, reducing cytoplasmic TNKS/TDP-43 co-localization, thereby releasing TNKS in the cytoplasm. Free TNKS gets associated with proteasome inhibitor of 31 kDa (PI31), reversing PI31-mediated inhibition of proteasome assembly, trafficking, and activity. Thus, FMRP regulates proteasome activity by modulating the subcellular distribution of TDP-43. Interestingly, FMRP expression is elevated in specific brain regions and spinal cords of TDP-43 transgenic ALS mice that helps more TDP-43 to stay in cytoplasm to sequester more TNKS with it, resulting in proteasome dysfunction in ALS disease system. We have demonstrated for the first time that FMRP can act as a disease modifier for ALS. ALS patients with high FMRP expression in the brain and spinal cord may exhibit more severe protein aggregation due to proteasome dysfunction. - Source: PubMed
Majumder PrithaAhsan AsmarBubphachat PitchapaAkter KhadizaHuang Jeffrey KHuang Chi-Chen Sarah - Endometrial cancer (EC) incidence continues to rise, underscoring the need for effective therapies beyond BRCA-mutant disease. Although PTEN loss, a frequent alteration in EC, has been implicated in impaired homologous recombination and increased sensitivity to PARP inhibitors, responses to PARP inhibitor monotherapy remain variable and are often limited by resistance mechanisms in PTEN-deficient tumours. Here, we show that the dual PARP/tankyrase (TNKS) inhibitor JPI-547 exerts potent antitumor activity, particularly in PTEN-deficient Ishikawa tumours. In vitro, JPI-547 and olaparib more effectively reduced cell survival in PTEN-deficient cells, and combined treatment with olaparib and the TNKS inhibitor XAV-939 induced synergistic cytotoxicity with elevated DNA double-strand breaks. Dual PARP/TNKS inhibition did not further suppress RAD51 but modulated non-homologous end joining and attenuated Wnt/β-catenin signalling in a PTEN-dependent manner. PTEN knockdown further showed enhanced vulnerability to combined targeting. These findings show that JPI-547 enhances antitumor efficacy in PTEN-deficient EC by disrupting DNA repair pathways and Wnt signalling, supporting dual PARP/TNKS inhibition as a potential therapeutic strategy and providing a rationale for further clinical evaluation. - Source: PubMed
Kang Sung WanEum HyerimLee Ji-YoungLee Min-SeoKim Yong-ManKim Tae WonLee Shin-Wha - SNAREs participate in tumor progression; however, existing studies on SNAREs remain fragmented. The discovery of suitable SNARE targets and delineation of their application limits are critical. - Source: PubMed
Publication date: 2026/06/08
Zhang YinghaoWang HaoranWang JinhaiSui YufangZhang WanhongLin XuhongZhang Pengpai