HIF2s

HIF2s, also known as Hypoxia-Inducible Factor 2, are a family of transcription factors that play a crucial role in cellular adaptation to low oxygen conditions, or hypoxia. They are part of a larger system that regulates gene expression in response to oxygen availability. HIF2s are heterodimers, meaning they are composed of two different protein subunits. One subunit is a constitutively expressed basic helix-loop-helix (bHLH) Per-Arnt-Sim (PAS) protein, often referred to as HIF-2α or EPAS1. The other subunit is a regulatory α-subunit that is hydroxylated and targeted for degradation under normal oxygen levels.

Under hypoxic conditions, the α-subunit is stabilized and translocates to the nucleus, where it binds to specific DNA sequences called Hypoxia Response Elements (HREs). This binding initiates the transcription of a variety of genes involved in processes such as erythropoiesis (red blood cell production), angiogenesis (formation of new blood vessels), glucose metabolism, and iron homeostasis. The HIF pathway is therefore essential for survival and function in oxygen-deprived environments. Dysregulation of HIF2s has been implicated in various pathological conditions, including cancer, where it can promote tumor growth and metastasis, and certain anemia types. Consequently, HIF2s are a significant target for therapeutic interventions.