Ask about this productRelated genes to: TNK1 antibody
- Gene:
- TNK1 NIH gene
- Name:
- tyrosine kinase non receptor 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-12-03
- Date modifiied:
- 2018-07-17
Related products to: TNK1 antibody
Related articles to: TNK1 antibody
- Lung cancer is a leading cause of cancer-related mortality, with current therapies limited by drug resistance and immunosuppressive tumor microenvironment (TME). Cuproptosis offers new therapeutic prospects, but effective induction and targeted delivery remain challenging. Herein, we developed xanthohumol (XN)-coordinated copper oxide/hyaluronic acid (XN@CuO/HA) nanobipyramids as a novel cuproptosis inducer for non-small cell lung cancer (NSCLC) therapy. XN@CuO/HA exhibited good colloidal stability, and potent antitumor activity by inducing mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and cuproptosis. Mechanistically, transcriptomic and functional analyses identified the FOXO1-GADD45G axis as a critical mediator of XN@CuO/HA-induced cuproptosis. , XN@CuO/HA significantly suppressed LLC xenograft growth in C57BL/6 mice with excellent biosafety. Moreover, it remodeled the immunosuppressive TME by enhancing CD8 T/NK1.1 cell infiltration and reducing MDSCs, synergizing with anti-PD-1 antibody to achieve superior antitumor efficacy. Collectively, our findings highlight XN@CuO/HA as a safe and effective nano-therapeutic that induces FOXO1-GADD45G-mediated cuproptosis and potentiates immunotherapy, providing a promising combinatorial strategy for NSCLC treatment. - Source: PubMed
Publication date: 2026/02/25
Jiang RuiyangHuang XiangmingOuyang YiranLuo BichongWan HongYangShou FangyangWu XiahuiFan JuntingZhang JingyuanSun DongdongXu ChangliangFang Zhijun - Fibrosis is a major challenge in glaucoma management, particularly following surgical interventions like trabeculectomy. In this study, we explored the therapeutic potential of a fibrosis-modulating peptide (VRF2019) and its mitomycin conjugate by evaluating their transcriptomic impact on primary Tenon fibroblast cells isolated from post-trabeculectomy tissues. To the best of our knowledge, this is the first comprehensive transcriptomic mapping of glaucoma-associated fibrotic fibroblasts, incorporating targeted drug delivery mechanisms. Fibroblasts were subjected to three conditions: Control (untreated), peptide treatment, conjugate treatment, and gene expression changes were analyzed through pairwise comparisons. Peptide-treated cells exhibited dysregulation in 231 transcripts, whereas conjugate-treated cells demonstrated more pronounced changes with 553 dysregulated transcripts. Comparisons between peptide- and conjugate-treated cells revealed 267 differentially expressed transcripts. Bioinformatic analysis highlighted key pathways affected by the treatments, including upregulation of IL-17, TNF-alpha, NF-kappa B, and Hippo signaling pathways, as well as suppression of protein phosphorylation and cell communication pathways. Kinase profiling revealed distinct and overlapping dysregulations across the conditions, with TGFBR1, EPHA2, and NUAK2 upregulated in peptide-treated cells, while conjugate treatment downregulated kinases such as PIM1, RET, and CAMKK1. Weighted gene coexpression network analysis identified significant hub genes, including TGFBR1 in the peptide-treated cells and TNK1 in conjugate-treated cells, elucidating key molecular players in fibrosis modulation. These findings demonstrate that the peptide and its conjugate exert significant antifibrotic effects by modulating transcriptional, signaling, and apoptotic pathways. The conjugate exhibited enhanced regulation of extracellular signaling and fibrotic pathways, suggesting its superior therapeutic potential. This study provides a foundational transcriptomic framework for advancing targeted therapies in glaucoma-associated fibrosis. - Source: PubMed
Publication date: 2025/09/26
Suresh Babu JayavigneeswariGaikwad Kiran BharatArumugam PavithraSharma JyotiElchuri Sailaja VGeorge RonnieJanakiraman Narayanan - Cholangiocarcinoma (CCA) is one of the most lethal cancers, characterized by molecular heterogeneity and treatment resistance. To uncover new biological signals and therapeutic opportunities, we employed multiomic characterization combined with machine learning. - Source: PubMed
Publication date: 2025/09/29
Mun Dong-GiJessen ErikTomlinson Jennifer LCarlson DanielleBudhraja RohitAlva-Ruiz RobertoAbdelrahman AmroWatkins RyanGregory LindseyMcCabe ChantalWang ChenGraham Rondell PWoods KathrynGolkowski MartinBaker MarshallGores Gregory JIlyas Sumera IConboy CaitlinLarson Ellen LSample Jack WOzmert Enis HKandasamy Richard KBorad Mitesh JRoberts LewisAndersen JoshuaPandey AkhileshSmoot Rory L - Fusing a variant of the sterile alpha motif domain of the human translocation ETS leukaemia protein (TELSAM) to a protein of interest has been shown to significantly enhance crystallization propensity. TELSAM is a pH-dependent, polymer-forming protein crystallization chaperone which, when covalently fused to a protein of interest, forms a stable, well-ordered crystal lattice. However, despite its success, a challenge persists in that crystal quality and diffraction limits appear to be heavily dependent on the choice of linker between TELSAM and the protein of interest, with identification of a functional linker relying on trial-and-error methods. Likewise, previous studies revealed that the 10xHis tag at the TELSAM N-terminus can either facilitate or hinder the ordered crystallization of target proteins attached via flexible or semi-flexible linkers. To address these challenges, we designed multiple constructs with several types of linkers-rigid (helical fusion), semi-flexible (Pro-Ala), and flexible (poly-Gly)-of varying lengths to fuse a designed ankyrin repeat protein (DARPin) to the TELSAM C-terminus. Semi-flexible and flexible linker constructs were made with and without the 10xHis tag. Our findings indicate that short semi-flexible and rigid linkers consistently yield large crystals within 24 hours with a DARPin target protein, but that flexible linkers perform best with a TNK1 UBA domain target protein. Removing the 10xHis tag enhanced crystallization rates, improved crystal morphology, and increased the crystallization propensity of semi-flexible and flexible linker constructs. While removing the His tag did not have a significant effect on crystal size, it improved the diffraction limits and crystal quality of the 1TEL-PA-DARPin construct. These results suggest that the ideal linker selection primarily depends on the properties of the target protein. Our data support the recommendation to use a short yet flexible or semi-flexible linker between TELSAM and the target protein to facilitate protein crystallization and high-resolution structure determination. - Source: PubMed
Publication date: 2025/09/02
Romo Maria Jose PedrozaKeliiliki AlihikauaAverett Jacob CGonzalez Joseph FNoakes EthanWilson Elijah WSmith ConradAverett BlakeHansen DaltonNickles RileyBradford MilesSoleimani SaraSmith TobinNawarathnage SupeshalaSamarwickrama PrasadikaKelsch ArielBunn DerickStewart CameronAbiodun WisdomTsubaki EvanBrown SethDoukov Tzanko IMoody James D - The androgen receptor (AR) signaling drives prostatic development and carcinogenesis, whereas the zinc finger homeobox 3 (ZFHX3) transcription factor modulates these processes. AR upregulates ZFHX3 transcription, but whether and how ZFHX3 plays a role in the AR signaling is unknown. RNA-seq was used to identify AR target genes that were also affected by ZFHX3 loss. Gene expression changes were verified using western blotting and qPCR. Immunoprecipitation, luciferase promoter-reporter assay, and western blotting were performed to assess ZFHX3's impact on AR transcriptional activity and ZFHX3 and AR protein interaction. Cell proliferation and colony formation assays were used to evaluate ZFHX3's impact on AR function. Kaplan-Meier analysis assessed the association of AR/ZFHX3 expression with patient survival. ZFHX3 loss in C4-2B/LNCaP cells downregulated classic AR target genes such as KLK3, FKBP5, and TMPRSS2 while upregulating some unclassical AR target genes (e.g., TNK1, ADAM7, and MAPRE2). ZFHX3 protein bound AR via multiple regions, particularly residues 1-223. ZFHX3 loss promoted cell proliferation/colony formation and attenuated enzalutamide's efficacy. Higher AR expression levels correlated with worse disease-free survival only in lower-ZFHX3 prostate cancer patients. Biochemically, ZFHX3's absence weakened AR's transactivity, including AR's binding to target gene promoters. These findings suggest that ZFHX3 is integral for AR signaling in prostate epithelial cells. ZFHX3 loss, which occurs in advanced prostate cancer, affects AR's function in gene transcription and could thus compromise PSA/KLK3 utility in prostate cancer detection. - Source: PubMed
Publication date: 2025/07/01
Fu XingZhang ZhiqianChen RuiA JunAn NaTian XinxinDong Jin-Tang