Ask about this productRelated genes to: ARNT antibody
- Gene:
- ARNT NIH gene
- Name:
- aryl hydrocarbon receptor nuclear translocator
- Previous symbol:
- -
- Synonyms:
- HIF-1beta, bHLHe2
- Chromosome:
- 1q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 1990-01-22
- Date modifiied:
- 2016-10-05
Related products to: ARNT antibody
Related articles to: ARNT antibody
- Induction of programmed cancer cell death by selective aryl hydrocarbon receptor (AHR) ligands represents a promising strategy for developing novel anticancer therapeutics. In this study, we characterized the anticancer activity and underlying mechanism of the selective AHR ligand CGS-15943 in lung cancer cells. CGS-15943 potently inhibited the growth of lung cancer cell lines expressing high levels of AHR, whereas CRISPR-mediated knockout of AHR in H460 and H69AR cells markedly rescued cells from CGS-15943-induced cell death, demonstrating an essential role for AHR. To identify additional mediators of this response, we performed a genome-wide CRISPR knockout screen, which revealed eight enzymes involved in the heme biosynthesis pathway, three heme-containing enzymes, as well as AHR and its transcriptional partner ARNT, as critical determinants of CGS-15943-induced cell death. Transcriptomic analyses further showed that CGS-15943 induced AHR-dependent transcriptional programs enriched for oxidative stress and oxidized phospholipid response pathways. Together, these findings identify key components of the AHR signaling network that regulate a programmed heme-dependent cell death pathway and establish CGS-15943 as a promising lead compound for targeting AHR-positive lung cancers. - Source: PubMed
Publication date: 2026/08/10
Nguyen Bach DKolluri Siva K - Juvenile hormone (JH) is vital to insects. In , JH signals through a basic helix-loop-helix-PER-ARNT-SIM (bHLH-PAS) protein methoprene-tolerant (MET) and its paralog germ cell-expressed (GCE). Binding of JH to the PAS-B domain of MET or GCE triggers the assembly of a DNA-bound, transcriptionally active JH receptor (JHR) heterodimer comprising either MET or GCE and their partner taiman (TAI). Molecular mechanisms of the JHR complex activation remain unclear. Here, we use the GCE protein to address the presumably critical but as yet unexplored function of the other PAS domain (PAS-A) in JHR signaling. We show that charged amino acid residues, highly conserved within the PAS-A domain across insect and mammalian bHLH-PAS proteins, are required for JHR signaling in vitro and in vivo. Mutations at these sites do not affect the ability of GCE to bind JH to its PAS-B domain. However, they compromise the JH-induced nuclear import of GCE, its dissociation from the chaperone heat-shock protein HSP83, and dimerization with TAI, consequently preventing the DNA binding and transcriptional JHR activities. Functionality of the mutated GCE variants in developing flies is also impaired. Molecular modeling suggests that mutations of the charged GCE PAS-A residues alter the natural salt bridges critical for intra- and interdomain interactions. This in turn causes non-native configurations of both GCE PAS domains, making them incompatible with TAI dimerization and possibly augmenting GCE attachment to HSP83. These results suggest that JHR signaling critically depends on interactions between PAS-A and PAS-B domains which are allosterically coupled. - Source: PubMed
Publication date: 2026/08/06
Bittova LenkaTumova SarkaYatsenko MykolaMokhamatam Raveendra BabuTuma RomanJindra Marek - Prostate cancer (PCa) is one of the most common cancers in males, and its treatment remains challenging due to the tumor microenvironment (TME) with immunosuppressive properties and limited response to anti-PD-1 therapy. Gut microbiota-derived metabolites have recently emerged as modulators of cancer immunometabolism, however, their role in PCa progression and immunotherapy is poorly understood. Here we found that indole-3-lactic acid (ILA), a metabolite produced by Lactobacillus plantarum, exerted dual anti-tumor effects on PCa cells and the TME. Mechanistically, ILA activates the aryl hydrocarbon receptor (AHR), and the resulting AHR/ARNT heterodimer translocates into the nucleus and binds to the promoter of ASF1B. This heterodimer then recruits the HDAC1/2-NuRD complex to reduce H3K27ac levels and suppress ASF1B expression. ASF1B binds to specific residues of ENO1 via its N-terminal core domain and enhances ENO1 enzymatic activity. ILA-induced downregulation of ASF1B impairs this interaction, reduces ENO1 activity, and suppresses the PI3K/Akt pathway, thereby inhibiting the malignant phenotypes of PCa cells. Concurrently, ILA decreased CXCL8 secretion by inhibiting the PI3K/Akt/NF-κB pathway, enhancing CD8 T cell infiltration and M1 macrophage polarization, thereby remodeling the TME. Additionally, ILA synergized with anti-PD-1 therapy to more effectively suppress tumor growth. These findings reveal a novel mechanism by which gut microbiota-derived metabolites regulate PCa progression and immunometabolism, positioning ILA as a potential therapeutic agent to improve PCa treatment. - Source: PubMed
Publication date: 2026/08/06
Wang ZhengshiJia ChengyouLiu YongqiangRixiati YoulutuziayiZhang WentaoMao ShiyuChen HaotianZou LibinYe ChenShen BingYao Xudong - Based on the hypoxia-inducible factor-1α(HIF-1α)/aryl hydrocarbon receptor nuclear translocator(ARNT) signaling pathway, this study aims to investigate the effects and potential mechanisms of artesunate in enhancing the effect of leflunomide on inhibiting bone destruction in rheumatoid arthritis(RA). By using in vitro osteoclast differentiation model induced by receptor activator of nuclear factor-κB ligand(RANKL) and a collagen-induced arthritis(CIA) mouse model, the intervention effect of combination treatment on bone destruction in RA was systematically evaluated at the cellular, histological, and molecular levels. Key mechanisms were analyzed and screened via transcriptomic sequencing, and relevant mechanisms were further validated through in vitro and in vivo experiments. The results show that artesunate can significantly enhance leflunomide's inhibitory effect on osteoclast formation, further reducing actin ring formation and bone resorption activity. In CIA mice, the combination treatment more effectively decreases the number of tartrate-resistant acid phosphatase(TRAP)-positive multinucleated osteoclasts in the joints compared with leflunomide alone, suggesting that artesunate potentiates leflunomide's ability to inhibit osteoclast formation and differentiation, thereby alleviating bone destruction in RA. Transcriptomic analysis indicates that artesunate may enhance leflunomide's inhibitory effect on bone destruction in RA by modulating the HIF-1α/ARNT signaling pathway. Further validation finds the nuclear co-localization of HIF-1α and ARNT during osteoclast differentiation. The combination treatment markedly suppresses HIF-1α/ARNT signaling and the expression of molecules related to downstream osteoclasts, while upregulating antioxidant-related proteins. The critical role of this signaling pathway in the combination treatment for inhibiting osteoclast differentiation is further supported by using an HIF-1α inhibitor. In summary, this study elucidated the critical role of the HIF-1α/ARNT signaling pathway in artesunate-enhanced leflunomide-mediated amelioration of bone destruction in RA, providing new experimental evidence and theoretical support for understanding the molecular mechanisms of bone destruction in RA and guiding combination treatment with leflunomide. - Source: PubMed
Huang Feng-YuChen Pei-PingDing Dai-YueWang QianLi Si-YuLin NaKong Xiang-YingSu Xiao-Hui - Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants associated with various health risks. They primarily enter the human body through food. The most toxic PAH is benzo[a]pyrene (BaP), which serves as a key marker in food safety regulations. In this study, a NanoBRET-based detection system was developed to evaluate the protein-protein interaction between aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) in response to BaP. BRET vectors encoding NanoLuc-fused AhR and HaloTag-fused ARNT were used to monitor heterodimer formation, and the optimal combination for BaP detection was selected. A cell-free assay was established to assess the biological activity of BaP by quantifying AhR/ARNT heterodimerization. This assay could be used for faster, simpler, and more biologically relevant toxicity evaluation than conventional methods. The assay was optimized to minimize protein consumption and enable high-throughput screening. Thus, this BRET-based platform provides a rapid and accurate method for detecting BaP in food safety applications. - Source: PubMed
Publication date: 2026/08/02
Seo AhreumSeo HyeyeongSeo HuiwonLee Seok-HeePark Yooheon