Ask about this productRelated genes to: TELO2 antibody
- Gene:
- TELO2 NIH gene
- Name:
- telomere maintenance 2
- Previous symbol:
- -
- Synonyms:
- KIAA0683, hCLK2, TEL2
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2006-09-25
- Date modifiied:
- 2014-11-19
Related products to: TELO2 antibody
Related articles to: TELO2 antibody
- Colorectal cancer is frequently driven by hyperactivation of Wnt/β-catenin signaling, which also contributes to reduced responsiveness to chemotherapy. However, how aberrant Wnt/β-catenin signaling enables colorectal cancer cells to tolerate chemotherapy-induced DNA damage remains elusive. Identifying actionable downstream effectors of this pathway may provide a more selective strategy to improve chemotherapy response while avoiding the toxicity associated with global Wnt inhibition. Here we show that TELO2-interacting protein 1 (TTI1) is a direct transcriptional target of β-catenin/TCF in colorectal cancer. TTI1 expression correlates with β-catenin abundance and is elevated in tumors from patients with poor response to neoadjuvant chemotherapy. Mechanistically, TTI1 maintains the integrity of the TELO2-TTI1-TTI2 complex and stabilizes the DNA damage response kinases ATM and ATR. Genetic depletion of TTI1 destabilizes ATM and ATR, attenuates DNA damage signaling, impairs double-strand break repair, and sensitizes colorectal cancer cells to 5-fluorouracil and oxaliplatin. Conversely, restoration of TTI1 or ATM/ATR re-establishes DNA damage responses and chemo-insensitivity. Pharmacological suppression of the TTT complex by piperlongumine mimics TTI1 loss and enhances the anti-tumor activity of chemotherapy in cell lines, xenografts, Apc-mutant patient-derived organoids and Apc colonic adenomas. These findings define a β-catenin-TTI1-ATM/ATR axis that links Wnt/β-catenin activation to DNA damage tolerance and chemotherapy response in colorectal cancer. Targeting TTI1 is therefore a promising approach to improve chemotherapy efficacy in Wnt/β-catenin-activated colorectal cancer. - Source: PubMed
Publication date: 2026/06/12
Chen YuqiaoChen ZhengWang YaYao YuanbingZhang YouyuHuang WentaoSong KunTan FengboLong FeiLin ChangweiZhang QianZhu WeiZhuang WeiZhou JianhuaLiu HeliXiao ShuaiFu Kai - PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, are traditionally regarded as germline factors that partner with PIWI-interacting RNAs (piRNAs) to silence transposons and regulate gene expression. However, growing evidence implicates PIWI proteins as oncogenic drivers in diverse somatic cancers, often acting through piRNA-independent mechanisms that remain incompletely understood. Here, we integrate transcriptomic, translatomic, and proteomic profiling of wild-type versus PIWIL1-knockout gastric cancer cells to uncover a non-canonical, translational role for PIWIL1, one of the four human PIWI proteins. We find that PIWIL1 selectively enhances the translation of 5'-terminal oligopyrimidine (TOP) mRNAs by activating mTOR complex 1 (mTORC1). Mechanistically, PIWIL1 interacts with the R2TP chaperone complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) and promotes its association with TELO2, facilitating mTOR-RAPTOR assembly and mTORC1 activation. Functionally, PIWIL1 deficiency sensitizes gastric cancer cells to mTOR inhibition, and in clinical samples, PIWIL1 expression positively correlates with mTORC1 pathway activity. Together, these findings define a novel piRNA-independent mechanism through which PIWIL1 contributes to tumor progression, extend PIWI-mediated translational control from the germline to human cancers, and establish PIWIL1 as a potential therapeutic target for gastric cancer in synergy with mTOR inhibition. - Source: PubMed
Publication date: 2026/04/22
Fan TianquZhao JiangshaLi LingCui MeihuaZhang JiaweiChi TianShi Shuo - Obesity exhibits a high heritability with heterogeneity; however, the genetic variants identified as obesity-causing factors are still underexplored. By performing deep sequencing on 2295 cases of young-onset obesity from East Asian populations and 2292 lean controls, we identified five genes (, , , , and ) with an excess burden of rare predicted loss-of-function (LoF) variants in cases. Among the variants, TUB p.R364G was identified as a potential deleterious variant that disrupted TUB protein's subcellular localization. Knock-in mice carrying the homologous p.R363G variant exhibited hyperphagia and obesity in an allele dose-dependent manner when fed a high-fat diet. The TUB p.R363G variant also blunted responses to leptin-induced suppression of food intake, leading to leptin resistance in mice. Furthermore, we demonstrated that TUB acted as a positive regulator of the leptin pathway through its interaction with STAT3, and this interaction was impaired by the p.R364G variant. TUB silencing mitigated the inhibitory effects of leptin on the activities of agouti-related protein (AgRP)-expressing neurons. Consistently, conditional ablation of TUB in AgRP neurons in mice led to hyperphagic obesity and attenuated leptin-induced appetite suppression in mice. Thus, our study demonstrates that rare LoF variants in TUB predispose to young-onset obesity in humans, likely through impairing leptin sensitivity in AgRP neurons. - Source: PubMed
Publication date: 2026/02/11
Tong MuyeChen YanruSong BeiteHong JieGu WeiqiongShen JuanYang HuanjieXia HuiminLi QianChen YufeiZhao ShaoqianLyu QianqianXue WenzhiMa QinyunZhou HoudeWu HuixuanGuo YihuaCao ZhiwenZhao YuxiaoZhang MinchunGu XuejiangZheng JieZhang YifeiLu JieliNing GuangBi YufangWang WeiqingLiu RuixinWang Jiqiu - To analyze the clinical manifestations and genotype of a child with You-Hoover-Fong syndrome (YHFS) to enhance clinical understanding of this disease. - Source: PubMed
Li PeiHuang YanruZhou YixiHu Shuxiang - - Source: PubMed
Publication date: 2026/01/19
Odabassian MelissaMyers Kenneth A