ARNT

ARNT, short for aryl hydrocarbon receptor nuclear translocator, is a transcription factor in the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) family. In humans, ARNT is also known as HIF-1β, reflecting its role as the dimerization partner for hypoxia-inducible factor 1α in the cellular response to low oxygen. As a versatile cofactor, ARNT forms heterodimers with multiple partner proteins, enabling distinct transcriptional programs in response to different signals.

Two major pathways illustrate ARNT's function. When paired with AHR (aryl hydrocarbon receptor), ARNT mediates the expression of xenobiotic-metabolizing enzymes such as CYP1A1, facilitating responses to environmental toxins. When paired with HIF-1α or HIF-2α (EPAS1), ARNT drives hypoxia-responsive gene expression that supports adaptation to low oxygen, including genes involved in angiogenesis, metabolism, and survival. ARNT also partners with certain circadian regulators, such as NPAS2, to influence circadian gene expression in specific tissues.

ARNT is widely expressed and essential for development. In animal models, loss of ARNT function disrupts development and is often embryonically lethal, underscoring its central role in integrating environmental and cellular signals. In humans, dysregulation of ARNT signaling has been linked to diseases characterized by altered oxygen sensing or xenobiotic metabolism, including cancer and metabolic disorders. ARNT is the subject of ongoing research, with attention to its potential as a therapeutic target in conditions driven by hypoxia or xenobiotics.