Ask about this productRelated genes to: TNIK antibody
- Gene:
- TNIK NIH gene
- Name:
- TRAF2 and NCK interacting kinase
- Previous symbol:
- -
- Synonyms:
- KIAA0551
- Chromosome:
- 3q26.2-q26.31
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-26
- Date modifiied:
- 2018-11-19
Related products to: TNIK antibody
Related articles to: TNIK antibody
- Acute myeloid leukemia (AML) is a heterogeneous malignancy rooted in hematopoietic stem cell dysregulation. Here, we identify the transcription factor Krüppel-like factor 4 (KLF4) as a potent suppressor of AML growth, with KLF4 overexpression markedly impairing AML cell proliferation. Mechanistically, KLF4 interacts with the lysine methyltransferase 2 C (MLL3/KMT2C) histone methyltransferase complex to activate transcription of nuclear receptor-binding protein 2 (NRBP2), a pseudokinase. Furthermore, integrated transcriptomic and functional analyses identify TNIK (TRAF2- and NCK-interacting kinase) as a pro-leukemic downstream effector restrained by the KLF4-NRBP2 axis. Pharmacological inhibition of TNIK with TNIK-IN-1 inhibits AML cell growth while exerting limited effects on normal hematopoietic cells. Together, these findings establish a KLF4/MLL3 complex-NRBP2 regulatory axis that restrains AML growth through suppression of TNIK expression and provide a rationale for further preclinical evaluation of TNIK inhibition as a therapeutic strategy in AML. Schematic model illustrating the mechanism by which the KLF4/MLL3 complex/NRBP2 axis regulates the progression of AML. In AML cells with basal KLF4 expression, higher expression of TNIK promotes the proliferation of AML cells (upper). Upon KLF4 overexpression, the TRD and ZnF domains of KLF4 bind to MLL3, which facilitates the recruitment of the MLL3 complex to the NRBP2 cis-regulatory regions. This activates NRBP2 transcription and subsequently downregulates TNIK expression, leading to the suppression of AML cell proliferation. Pharmacological inhibition of TNIK by TNIK-IN-1 reduces TNIK protein levels, represses AML cell growth, and induces cell apoptosis (lower). This study reveals a molecular mechanism by which KLF4 governs AML progression, providing a novel therapeutic target and a potential small-molecule inhibitor for AML treatment (Created in BioRender. he, Y. (2026) https://BioRender.com/q0q3j3q ). - Source: PubMed
Publication date: 2026/09/02
Yang MengLu TingHe YichengChen CongWang YifeiSun GuohuanZheng YaweiQin JiaxinYe JialiXie XiaoweiZhao XiangnanDuan HonglinZhang BiaoLi YapuDong FangXu ChangCheng TaoCheng HuiYang Shangda - In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrete human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) to profile the proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell-type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1, and TNIK, that are essential for maintaining the hTSC stem-state. Additionally, atypical protein kinase C isoforms PKCζ are essential for STB development, whereas PTK2B, SRC, TRIO, and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy. - Source: PubMed
Kumar RajnishDasgupta PurbasaRay SomaPaul Soumen - Natural product scaffolds provide structurally distinctive starting points for anticancer small-molecule discovery, yet connecting phenotype-guided optimization with molecular target identification remains challenging. Here, focused diversification of a previously reported sophoridine-derived aminoquinoline scaffold, followed by cell-based screening, led to the identification of YM17 as a potent anti-hepatocellular carcinoma (HCC) analogue. YM17 inhibited HuH-7 cell proliferation with an IC value of 0.50 μM and exhibited antitumor activity across cellular phenotypic assays and an HCC xenograft model. Single-temperature thermal proteome profiling nominated TNIK as a candidate target of YM17. Orthogonal validation showed that YM17 increased the thermal stability of TNIK in cells, inhibited recombinant TNIK kinase activity with an IC value of 181.9 nM, and bound to TNIK in a surface plasmon resonance assay. Mechanistic analyses further revealed changes in TNIK-associated proliferative signaling and apoptosis-regulatory proteins that were consistent with the observed anti-HCC phenotype. Collectively, these findings identify YM17 as a potent sophoridine-derived TNIK inhibitor with cellular target engagement and in vivo anti-HCC activity. This work also highlights the value of integrating phenotype-guided natural product scaffold diversification with proteome-scale target deconvolution for anticancer lead discovery. - Source: PubMed
Publication date: 2026/08/22
Wei YongquanWang ZiyiSun DieXing ZexuYu HaixiaWang Lisheng - Macrocyclization strategies that generate conformationally constrained peptide scaffolds within nucleotide-encoded library screening platforms have significantly advanced the discovery of de novo bioactive peptides. We previously reported ribosomal synthesis of topologically defined thioisoindole-bridged bicyclic (TiB) peptides, but complete conversion required overnight incubation. Here, we reengineer the key ribosomally incorporated substrate to accelerate TiB formation to full conversion within 2 h. This was followed by a streptavidin-based pulldown step to efficiently remove linear species and purify the desired TiB peptides. The optimized chemistry was incorporated into the RaPID (Random nonstandard peptides integrated discovery) system to enable de novo identification of TiB peptide ligands. As a proof of concept, two complementary TiB libraries were screened against Traf2- and NCK-interacting kinase (TNIK). Of the five TiB candidates identified, four exhibited nanomolar affinity for TNIK (best K = 12.3 nM), and the most potent ligand, TK7, inhibited TNIK kinase activity with an IC of 60 nM. X-ray crystallography revealed that TK7 adopts a unique binding mode on the TNIK surface. Collectively, these findings establish a practical platform for TiB peptide discovery, highlighting their potential in early-stage peptide drug development. - Source: PubMed
Publication date: 2026/08/13
Zhang YueVinogradov Alexander AHamada KeisukeSun YinSengoku ToruSuga Hiroaki - In the developing human placenta, three subtypes of trophoblast cells, cytotrophoblasts (CTBs), extravillous trophoblasts (EVTs), and syncytiotrophoblasts (STBs), mediate critical functions essential for a successful pregnancy. CTBs constitute the stem/progenitor compartment and differentiate into STBs and EVTs within the floating and anchoring villi, respectively. STBs establish the maternal-fetal exchange interface and secrets human chorionic gonadotropin (hCG), a hormone vital for the maintenance of early pregnancy. EVTs anchor the maternal endometrium and invade the uterine tissue to remodel maternal cells, supporting implantation and progression of pregnancy. In this study, we used human trophoblast stem cells (hTSCs) as a model system and performed quantitative, label-free liquid chromatography tandem Mass Spectrometry (LC/MS/MS) to profile proteome and phosphoproteome in TSC stem state (analogous to undifferentiated CTBs) and following their differentiation to STBs and EVTs. Through a multiomics approach, we integrated our proteomics data with global gene expression profiles to correlate cell type specific gene and protein expression during human trophoblast development. We also identified global phosphoproteome and analyzed kinases that are specifically active in hTSC stem state, as well as in differentiated STBs and EVTs. We experimentally validated specific kinases, such as BUB1B, PAK6, PKYMT1 and TNIK are essential for maintaining the hTSC stem state. Additionally, atypical protein kinase C isoforms PKC zeta is essential for STB development, while PTK2B, SRC, TRIO and LYN are important for EVT development. Our findings highlight key kinases uniquely required for specific stages of trophoblast development during human placentation and suggest that pharmacological inhibition of these kinases could negatively impact the placentation process during pregnancy. - Source: PubMed
Publication date: 2026/07/24
Kumar RajnishDasgupta PurbasaRay SomaPaul Soumen