Ask about this productRelated genes to: POU2F1 antibody
- Gene:
- POU2F1 NIH gene
- Name:
- POU class 2 homeobox 1
- Previous symbol:
- OTF1
- Synonyms:
- OCT1
- Chromosome:
- 1q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 1989-03-09
- Date modifiied:
- 2016-04-25
Related products to: POU2F1 antibody
Related articles to: POU2F1 antibody
- The circadian clock component PER2 coordinates daily oscillations in gene expression across multiple tissues, yet its role in assembling multi-protein regulatory complexes remains incompletely understood. Here, we report that PER2 nucleates a ternary complex with the tumor suppressor BRCA1 and the transcription factor POU2F1(OCT-1) to impose circadian control on target gene promoters. Using bacterial two-hybrid screening, we identified BRCA1 as a novel PER2-interacting protein. Biochemical mapping revealed that PER2 engages BRCA1 through multiple discrete binding interfaces: PER2 spanning residues 356-574 and 683-872 interact with both the N-terminal (1-400) and C-terminal BRCT (1670-1863) domains of BRCA1. Structural modeling predicted 361 residue contacts between PER2 and BRCA1, substantially more than the 74 contacts predicted for PER2:POU2F1(OCT-1), indicating differential affinities that enable ordered complex assembly. Sequential pull-down assays demonstrated that PER2, BRCA1, and POU domain form a stable ternary complex , with POU2F1(OCT-1) serving as the DNA-binding platform. Electrophoretic mobility shift assays revealed that pre-assembly of PER2 with POU domain inhibits DNA binding, while BRCA1 is essential for stabilizing PER2 recruitment to DNA-bound POU2F1(OCT-1). Using as a functional readout, we demonstrated that this ternary complex directly regulates promoter activity. Circadian transcriptome analysis revealed that exhibits robust clock-dependent oscillations that are abolished in double-knockout mice, while and maintain constitutive expression. These findings establish PER2 as a circadian scaffold that assembles multivalent protein complexes to temporally gate transcription, providing mechanistic insight into how circadian disruption can influence target gene expression. - Source: PubMed
Publication date: 2025/11/30
Kadukhina ElizavetaJia SiqiVilla Linda MYi XiaoCapelluto Daniel G SBriganti Jonathan SBrown Anne MFinkielstein Carla V - Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, yet the underlying mechanisms driving its progression are not fully elucidated. Long non-coding RNAs (lncRNAs) have recently emerged as key regulatory molecules in tumor biology. In this study, we identified ABHD11-AS1 as a tumor-suppressive lncRNA that is significantly downregulated in CRC tissues, its low expression is correlated with poor patient prognosis. Functional assays demonstrated that ABHD11-AS1 inhibits CRC cell proliferation, migration, and invasion, and enhances sensitivity to oxaliplatin. Mechanistically, ABHD11-AS1 directly binds to EIF4E and disrupts its phase separation, thereby suppressing the translation of USP18, a deubiquitinating enzyme that stabilises the oncogenic protein POU2F1. Reduced USP18 expression leads to increased ubiquitination and proteasomal degradation of POU2F1, ultimately inhibiting malignant progression and enhancing chemotherapy sensitivity. Collectively, our findings uncover a previously unrecognised mechanism by which ABHD11-AS1 modulates EIF4E-mediated phase separation to regulate protein homeostasis, highlighting its potential as a therapeutic target in CRC. - Source: PubMed
Publication date: 2026/04/23
Li ShizhenJiang XianjieOyang LindaXia LongzhengTan ShimingRen ZongyaoPeng QiuLin JinguanLiao QianjinZhou Yujuan - Exploring the targeted regulatory effect of isorhynchophylline on lipopolysaccharide (LPS)-induced acute lung injury (ALI) by constructing a drug delivery system of GEF-modified exosomes derived from M2 macrophages (M2-Exos) loaded with isorhynchophylline (GEF-M2-Exos-IRN; GMI). - Source: PubMed
Publication date: 2026/05/14
Zou Jin-RuYang DanZhang Chuan-MingZhang LuZhang Hao-NanSong MiaoMa Jun-BingYang ZhengQiu Min - Epstein-Barr virus (EBV) latent infection is causally linked to several epithelial cancers, including endemic forms of undifferentiated nasopharyngeal carcinoma (NPC), and to a subtype of gastric cancer (GC). EBNA1 is the virus-encoded sequence-specific DNA-binding protein required for episome maintenance but also contributes to host-cell survival through multiple mechanisms, including binding to the host chromosome. We previously developed small-molecule inhibitors of EBNA1 DNA-binding that block host cell cycle progression and growth of EBV+ cell lines and tumor models . However, the underlying molecular mechanisms of EBNA1 function and inhibition have not been completely elucidated. In this study, we employ VK1727 to inhibit EBNA1 DNA-binding to viral and cellular genomes in three EBV+ epithelial tumor-derived cell models (patient-derived xenograft C15, C666-1, and SNU719). We integrate EBNA1 ChIP-seq and transcriptomic RNA-seq analyses to identify the cell cycle-dependent kinase CDC7 and a stem cell transcription factor POU2F1 as direct functional targets of EBNA1 in each of these epithelial cancer models. EBNA1 binding to the CDC7 promoter and POU2F1 intron promotes RNA Pol II-pS5 to initiate transcription of these two genes. We show that CDC7 inhibitor simurosertib phenocopies VK1727, while Bcl-2 inhibitor venetoclax shows a synergistic effect with VK1727 for inhibition of EBV+ epithelial cancer cell proliferation and survival. Our study reveals new functional gene targets and pathways of VK1727 in EBV+ epithelial cancers that provide new biomarkers and combinatorial strategies to treat EBV-driven cancers. - Source: PubMed
Publication date: 2026/05/14
He SongtaoTerhuja NisenoSoldan Samantha SChen ChristopherCassel JoelYin XiangfanLiu QinChung Sun SookCastro-Muñoz Leonardo JosuéYoon LeenaWang JieSalvino Joseph MGewurz Benjamin ETempera ItaloMessick Troy ELieberman Paul M - Genetic variants in drug transporter genes shape the interindividual variability in drug response. However, their functional interpretation has remained limited due to the substrate dependence of variant effects. Existing predictors are substrate-agnostic and cannot capture how a single amino acid change differentially affects transport across drugs. Here, we present the substrate-specific effect predictor (SSEP), the first model to predict transporter variant effects in a substrate-dependent manner. SSEP integrates curated in vitro uptake assays with deep mutational scanning data, leveraging multiscale features extracted from modeled variant-substrate complexes. Based on a feed-forward deep neural network architecture, SSEP provides quantitative, substrate-specific activity scores that correlate with experimental uptake data (Spearman's ρ = 0.64) across multiple transporter families (OCT1, MATE, CNT, and OATP) and substrate classes (biguanides, tetraethylammonium, selective serotonin agonists, sympathomimetics and opiates). In benchmarking analyses, SSEP showed higher concordance (Kruskal-Wallis p = 1.11 × 10) with experimental uptake than commonly used substrate-agnostic predictors. Application of SSEP on UK Biobank data revealed that OCT1 (SLC22A1) variant burden weighted by metformin-specific SSEP scores was significantly associated with maintenance dose (β = 30 mg/day per unit increase in predicted functional burden; p = 0.033), whereas substrate-agnostic weights showed no association (p = 0.78). Together, these results show that SSEP enables quantitative, drug-specific prediction of transporter variant effects, thereby improving the identification of clinically relevant transporter variants in population-scale data. - Source: PubMed
Park YoomiZhou YitianXiao MingNies Anne TLauschke Volker M