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
- Bacterial infections often occur in polymicrobial biofilms where nutrient limitation and interspecies interactions can profoundly shape microbial physiology. can antagonize growth under conditions of iron limitation, such as those found in the mammalian host. Here, we report that this growth antagonism reveals surviving cells capable of surviving antibiotic challenge, including ampicillin, cefepime, and ciprofloxacin, when grown in iron-restricted biofilms with . Transcriptomic profiling of revealed a distinctive response characterized by broad downregulation of biosynthetic, metabolic, and virulence pathways, alongside selective induction of membrane remodeling proteins, transport systems, and biofilm-associated genes. Induction of in , required for lipid A modification, correlated with enhanced antibiotic survival to ampicillin, cefepime, and ciprofloxacin. Additionally, the diguanylate cyclase SiaD and efflux transporter MfsC in were implicated in decreased antibiotic susceptibility to the same antibiotics. This transcriptional response was unique to the dual stress of iron deprivation and microbial competition with , illustrating how interspecies interactions can simultaneously inhibit and protect , shedding light on potential persistence mechanisms in iron-limited polymicrobial environments.IMPORTANCEThis study addresses antibiotic susceptibility in , a major opportunistic ESKAPE pathogen, within polymicrobial biofilms and under host-relevant iron-restricted conditions. Polymicrobial biofilm-associated infections are notoriously difficult to treat due to complex interspecies interactions and increased antibiotic resilience. We demonstrate that not only antagonizes growth under iron limitation but also induces a unique transcriptional profile, enhancing survival during antibiotic challenge. This shift involves broad transcriptional reprogramming in , characterized by global metabolic downregulation and activation of envelope remodeling pathways, including the operon. These findings reveal how interspecies interactions under iron stress can both suppress and protect bacterial pathogens and underscore the importance of considering community context in treatment strategies for persistent infections. - Source: PubMed
Publication date: 2026/04/30
Anderson Caleb MMattenberger YvesParga AnaPortalier HeidiTan Casandra Ai ZhuEsteban Henao MariaViollier Patrick HKline Kimberly A - The molecular glue degrader field is growing rapidly, with multiple next-generation candidates in development. Some are targeted against culprit proteins not readily accessible to small-molecule inhibitors, such as ARNT; others aimed at ALK, for instance, may help address the resistance to existing tyrosine kinase inhibitors that inevitably occurs. - Source: PubMed
Publication date: 2026/04/29
- Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that coordinate cellular responses to low oxygen levels by binding a short hypoxia response element (HRE) DNA sequence near O-regulated genes. Prior studies suggest HIF/HRE complexes are augmented by the binding of additional factors nearby, but those interactions are not well understood. Here, we integrated structural and biochemical approaches to investigate several functionally relevant HIF assemblies with other protein, small molecule, and DNA partners. First, we used cryo-electron microscopy (cryo-EM) to establish that HIF-1 and HIF-2 self-assemble into "dimer-of-heterodimers" (DoHD) complexes on extended human EPO enhancer sequences, with one heterodimer bound at a canonical HRE site and the second binding in an inverted fashion to an HRE-adjacent sequence 8 bp away. Consistent with ARNT PAS-B domains predominating interactions within a DoHD, we found HIF-1 and HIF-2 coassemble mixed DoHD complexes on the same DNA. Second, we saw that despite the increased complexities of the larger complexes, ligands for the isolated ARNT or HIF-2α PAS-B domains still bound and disrupted both heterodimeric and DoHD complexes, albeit with variable potencies depending on the ligand. Finally, we combined cryo-EM and hydrogen-deuterium exchange by mass spectrometry (HDX-MS) to show how HIF-1 and HIF-2 heterodimers engage the transforming acidic coiled-coil containing protein 3 coactivator via both ARNT and HIF-α subunits, though this was unseen in the larger DoHD. Our findings highlight the importance of molecular context in biomolecular complex formation, adding to the complexities of potential regulation. - Source: PubMed
Publication date: 2026/04/28
Closson Joseph DXu XingjianZhang MeilingTiyani Tarsisius TMarcelino Leandro PimentelIsiorho Eta ANagati Jason SGarcia Joseph AGardner Kevin H - Pinealectomy leads to melatonin deficiency, which is known to disrupt circadian clock regulation and may increase vulnerability of the hippocampus to oxidative stress and neuroinflammatory processes. The objective of this study was to examine the gene expression levels of circadian locomotor output cycles kaput (CLOCK), brain and muscle ARNT-like 1 (BMAL1), period circadian regulator 1 (PER1), cryptochrome circadian regulator 1 (CRY1), brain-derived neurotrophic factor (BDNF), and interleukin-6 (IL-6) in the hippocampus to elucidate the impact of pinealectomy-induced circadian dysregulation on these gene expressions and to assess its association with hippocampal alterations. A total of 30 Wistar rats were randomly divided into three groups: Control, Sham, and Pinealectomy (PNX) ( = 10 per group). Gene expression levels were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis was performed to assess caspase-3 and glial fibrillary acidic protein (GFAP) immunoreactivity. In addition, oxidative stress parameters, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), as well as the inflammatory marker tumor necrosis factor-alpha (TNF-α), were measured. The pinealectomy group showed a significant downregulation of BMAL1, BDNF, CLOCK, CRY1, and PER1 gene expression levels, with decreases ranging from approximately 60% to 83% compared with the sham and control groups, whereas IL-6 expression was significantly increased by approximately 185% ( < 0.05). Immunohistochemical analysis demonstrated significantly increased caspase-3 and GFAP immunoreactivity in the PNX group. Furthermore, pinealectomy resulted in a significant increase in MDA and TNF-α levels, accompanied by marked decreases in SOD, CAT, and GSH levels ( < 0.05). In conclusion, pinealectomy is associated with significant disruption of hippocampal circadian clock gene expression, accompanied by oxidative stress, neuroinflammation, and histopathological alterations. These findings highlight the critical role of circadian regulation in maintaining hippocampal cellular integrity. - Source: PubMed
Publication date: 2026/04/21
Gurbuz Can VenharDemir MehmetKusat TansuBasak Feyza - BMAL1 is a bHLH-PAS transcription factor complex that utilizes its bHLH (basic helix-loop-helix) domains to bind E-box motifs in DNA and tandem PAS (PER-ARNT-SIM) domains to heterodimerize and interact with regulatory proteins to generate circadian rhythms. PAS domains are evolutionarily conserved modules that frequently bind small molecule ligands within buried cavities to perform sensory and signal transduction functions. CLOCK and BMAL1 PAS domains have cavities that could be leveraged to regulate the transcription factor, and consequently, the circadian clock. Using NMR spectroscopy, we identified small molecules that bind within a cavity inside the PAS-A domain of CLOCK and its paralog NPAS2, which sits at an important flexible junction in the structured core of the heterodimer. We identified a gatekeeping mutant in the core of CLOCK PAS-A that significantly decreased ligand binding affinity. High-pressure NMR studies showed that ligand binding or the gatekeeping mutant significantly stabilized the domain. Finally, we showed that ligands induced dose-dependent displacement of CLOCK:BMAL1 from DNA . Together, these data demonstrate that small molecules can regulate DNA binding by the circadian transcription factor CLOCK:BMAL1 through occupancy of a PAS domain cavity. - Source: PubMed
Publication date: 2026/04/14
Sharma DikshaBoral SoumenduWest EthenKressman McClainFranco IreneTripathi SarvindLee Hsiau-WeiAmezcua Carlos AFavaro Denize CGardner Kevin HPartch Carrie L