ARNT/HIF-1 beta Products

Description

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

Bioinformatics

Entrez	11863 Mouse 25242 Rat 405 Human
Uniprot	AAH60838 Human NM_001668 Human NP_001659 Human NP_001659.1 Human P27540 Human
Product By Gene ID	405
Alternate Names	ARNT protein ARNT aryl hydrocarbon receptor nuclear translocator BHLHE2 Class E Basic Helix-Loop-Helix Protein 2 Dioxin Receptor, Nuclear Translocator HIF-1 Beta HIF1B HIF1BETA HIF-1beta HIF-1-beta HIF1-beta hypoxia-inducible factor 1, beta subunit Hypoxia-inducible factor 1-beta TANGO

Research Areas for ARNT/HIF-1 beta

Find related products by research area and learn more about each of the different research areas below.

Angiogenesis
Autophagy
Cancer
Cellular Markers
Chromatin Research
HIF Target Genes
Hypoxia
Transcription Factors and Regulators

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HIF-2 alpha: HIF1A's Homologue with Similar and Divergent Functions HIF-2 alpha is a member of the heterodimeric hypoxia-inducible factors/HIFs family (HIF-1, HIF-2, and HIF-3) which contains a common beta subunit but differ in their alpha subunits. Also called as EPAS1 or Mop2, HIF-2 alpha regulates cellular adapt...    Read more.

HIF-1 beta - activating gene transcription in response to hypoxia Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor consisting of alpha and beta subunits. The levels of functional HIF-1 in the cell depends on the level of oxygen allowing cells to respond to hypoxic conditions. HIF-1a is a...    Read more.

HIF-3 alpha: a versatile target with hypoxia dependent and independent functions By: Subhash GangarHIF-3 alpha (hypoxia-inducible factor 3-alpha/ HIF3A) represents an isoform of HIF-alpha subunits which heterodimerize with stable beta subunit (HIF-beta) for the regulation of HIF target genes through binding to hypoxia respon...    Read more.

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