ARNT/HIF-1 beta Antibody (H1beta234) [Alexa Fluor® 750]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

Aryl hydrocarbon nuclear translocator (ARNT), also commonly known as Hypoxia-inducible factor 1-beta (HIF-1 beta), is a ubiquitously expressed transcription factor that is part of the basic-helix-loop-helix (bHLH)-Per-ARNT-Sim (PAS) family (1, 2). Human arnt is located on chromosome 1q21 and encodes a protein 789 amino acids (aa) in length with a theoretical molecular weight of 87 kDa (1). Structurally, ARNT has a DNA binding bHLH domain, two PAS domains required for dimerization, and a transactivation domain/PAC region (1). ARNT belongs to the Class II bHLH-PAS proteins and is able to homodimerize or heterodimerize with the Class I proteins including AHA, AHRR, HIF-1 alpha, HIF-2 alpha, NPAS1, and SIM1 (2). Dimerization allows for efficient DNA binding and regulation of their target genes (2).

ARNT has an important role in two specific signaling pathways - the aryl hydrocarbon receptor (AhR) and the hypoxia inducible factor (HIF) pathway (1). In the AhR pathway, AhR in the cytosol is typically inactive and bound to heat shock protein 90 (hsp90) (3). Upon activation and ligand binding by environmental pollutants such as dioxins, AhR is translocated to the nucleus, dissociates from hsp90, and dimerizes with ARNT, leading to binding to response elements and expression of target genes including monooxygenases (1, 3). In the HIF pathway, under hypoxia (low oxygen) conditions prolylhydroxylase domain (PHD) enzymes and factor inhibiting HIF (FIH) are inhibited. HIF-1 alpha (or HIF-2 alpha) accumulates and is transported to the nucleus where it heterodimerizes with ARNT, allowing for binding to target gene's hypoxia response element (HRE), recruitment of coactivators, and transcription (1, 3). HIF-induced gene transcription plays a large role in tumor progression by promoting invasion, metastasis, de-differentiation and altered metabolism, and angiogenesis (1). While HIF-1 alpha's stability is dependent upon oxygen conditions, HIF-1 beta is stable in both normoxia and hypoxia (1-3).

The bHLH-PAS family and ARNT have been linked with a variety of pathologies and diseases including cancer, metabolic diseases, autoimmune diseases, and psychiatric disorders (2). ARNT/AHR is expressed in the skin and its pathway activation enhances skin barrier function and epidermal terminal differentiation, thus AHR agonists are currently being used as therapeutics for atopic dermatitis and psoriasis (4). Accordingly, studies of Arnt-deficient mice show profound abnormalities in skin barrier function and keratinization (4). Additionally, studies suggest that ARNT plays an important role in diabetes and beta-cell function (5). Islets from patients with type 2 diabetes have a significantly decreased ARNT expression compared to glucose-tolerant control donors (5). Modulation and stimulation of the HIF pathway may be a potential therapeutic strategy for treating type 2 diabetes and metabolic syndrome (5).

Alternate names for ARNT/HIF-1 beta include aryl hydrocarbon receptor nuclear translocator, BHLHE2, class E basic helix-loop-helix protein 2, Dixon receptor nuclear translocator, Hypoxia-inducible factor 1-beta, nuclear translocator, and TANGO.

References

1. Mandl, M., & Depping, R. (2014). Hypoxia-inducible aryl hydrocarbon receptor nuclear translocator (ARNT) (HIF-1beta): is it a rare exception?. Molecular medicine (Cambridge, Mass.). https://doi.org/10.2119/molmed.2014.00032

2. Wu, D., & Rastinejad, F. (2017). Structural characterization of mammalian bHLH-PAS transcription factors. Current opinion in structural biology. https://doi.org/10.1016/j.sbi.2016.09.011

3. Esser, C., & Rannug, A. (2015). The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacological reviews.https://doi.org/10.1124/pr.114.009001

4. Furue, M., Hashimoto-Hachiya, A., & Tsuji, G. (2019). Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. International journal of molecular sciences. https://doi.org/10.3390/ijms20215424

5. Girgis, C. M., Cheng, K., Scott, C. H., & Gunton, J. E. (2012). Novel links between HIFs, type 2 diabetes, and metabolic syndrome. Trends in endocrinology and metabolism: TEM, https://doi.org/10.1016/j.tem.2012.05.003

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

Array NB100-124AF750

• ARNT/HIF-1 beta Antibodies
• ARNT/HIF-1 beta Antibody Pack
• ARNT/HIF-1 beta ELISA Kits
• ARNT/HIF-1 beta Lysate
• ARNT/HIF-1 beta Proteins