HIF-1 beta: A dimerization partner of HIF-1 alpha required for an adaptive response to hypoxia

Hypoxia contributes significantly to the pathophysiology of major categories of human disease, including myocardial and cerebral ischemia, cancer, pulmonary hypertension, congenital heart disease and chronic obstructive pulmonary disease. Hypoxia-inducible factor 1 (HIF-1) is a nuclear protein involved in mammalian oxygen homeostasis. It is a heterodimer composed of HIF-1 alpha and HIF-1 beta subunits which are bHLH proteins of PAS (PER, ARNT, SIM) family. HIF-1 beta forms heterodimer with AHR, AHRR, HIF-1 alpha and EPAS1/HIF-2 alpha as well as with other bHLH proteins and its dimerization is required for efficient DNA binding.

HIF-1 beta is encoded by the ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator) gene. It is able to partner with AhR to form a heterodimeric transcription factor complex which is required for AhR activity. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH pro-carcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia.

Hypoxia-inducible factor 1 (HIF-1) is critically involved in cancer cell hypoxia adaptation, glycolysis, and angiogenesis. HIF-1 beta is associated with HIF-1 functions as a dimerization partner of HIF-1 alpha, and is on the other hand associated with carcinogenesis via dioxin signaling. A study using Novus' HIF-1 beta antibody (NB100-124) suggested that HIF-1alpha and beta share common signaling pathways for nuclear protein accumulation. Regulation of HIF-1beta protein expression was investigated in human prostate cancer (PCA) cells. (1)

The Ah receptor nuclear translocator protein (ARNT) is required for Ah receptor function. ARNT is shown to be a structural component of the XRE binding form of the Ah receptor. Furthermore, ARNT and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. Arnt contains a basic helix-loop-helix motif, which may be responsible for interacting with both the XRE and the ligand-binding subunit. (2)

Bio-Techne offers HIF-1 beta reagents for your research needs including:

• HIF-1 beta primary antibodies
• HIF-1 beta lysates
• HIF-1 beta peptides and proteins
• HIF-1 beta antibody packs

• HIF-1 beta RNAi

PMIDs:

1. 11394885
2. 1317062