Aryl hydrocarbon receptor nuclear translocator (ARNT) (ARNT)

Aryl hydrocarbon receptor nuclear translocator (ARNT), also known as HIF-1 beta, is a critical transcription factor belonging to the basic helix-loop-helix-PAS family [1]. It serves as an essential heterodimeric partner for several alpha-subunits, including the Aryl Hydrocarbon Receptor (AHR) and Hypoxia-Inducible Factor 1-alpha (HIF-1α) [2]. By forming these complexes, ARNT facilitates the translocation of its partners to the nucleus and enables binding to specific DNA response elements [1]. This process regulates the expression of genes involved in xenobiotic metabolism, angiogenesis, and cellular adaptation to hypoxia [3]. In many cancers, ARNT is a key driver of the hypoxic response, promoting tumor survival, metabolic reprogramming, and resistance to therapy [3]. Beyond oncology, ARNT has been implicated in the maintenance of pancreatic beta-cell function, with its downregulation linked to the development of type 2 diabetes [4]. Therapeutic strategies targeting ARNT include small molecule inhibitors of its dimerization domains and RNA-based approaches, such as antisense oligonucleotides or siRNA, designed to reduce ARNT mRNA levels [5, 6]. Because ARNT is a common partner for multiple pathways, its inhibition can simultaneously disrupt several disease-promoting signals [6]. However, the ubiquitous expression and fundamental physiological roles of ARNT present significant challenges for achieving a safe therapeutic window [1, 2]. Sources: [1] UniProt (P27540) [2] NCBI Gene (405) [3] PMID: 15155833 [4] PMID: 16007090 [5] PMID: 25939391 [6] PMID: 26300478

Other names

HIF-1 betaHIF1BHypoxia-inducible factor 1-betabHLHe2TANGO

Inhibition of heterodimerization with HIF-1 alpha or AHR, or degradation of ARNT mRNA to prevent protein synthesis.