HIF-2 alpha

By Jamshed Arslan Pharm.D.

By Bethany Veo, PhD

Traumatic brain injury (TBI) currently contributes to nearly 30% of all injury deaths in the United States.  Characterized by an abrasive head injury that interrupts normal brain function, TBI can range from mild to severe.  Mild symptoms can present themselves as excessive tiredness, difficulty concentrating and lack of clear thinking.  Severe cases of TBI are hallmarked by unusual behavior, seizures and loss of consciousness.  Research has shown that on a molecular level TBI triggers various mechanisms of cell death alongside attempted tissue recovery, therefore Choi et al sought

HIF-2 alpha, also known as hypoxia-inducible factor 2, endothelial PAS domain protein-1, and member of PAS superfamily 2 is part of the HIF family of proteins.  The HIF family is composed of HIF-1, HIF-2 and HIF-3, where HIF-2 is a dimeric protein that consists of an alpha and beta subunit.HIF-2 alphais activated in the presence of oxygen deprivation, or hypoxia, via prolyl hydroxylase-domain enzymes (PHD

Hypoxia inducible factor 1 (HIF-1) is a protein that plays an essential role in hypoxia, or low levels of cellular oxygen.

Ki67, also known as MKI67, is best known as the leading marker of cellular proliferation. Ki67 is regulated by a balance between synthesis and degradation, and often carries a very short half-life.  First discovered to be located to dividing cells, Ki67 has since been specifically localized to the G1, S, G2 and M phases of mitosis. Soon after, it was discovered that there was a high correlation of Ki67 alongside the p53 (tumor suppressing protein 53), suggesting an implication in cancer. What’s more, the expression of Ki67 is higher in malignant cells versus control cells.

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.

By: Subhash Gangar

HIF-2 alpha is one subunit within the HIF-2 nuclear protein that regulates cellular responses to hypoxia (low oxygen tension conditions). Hydroxylation post-translational modifications on particular HIF residues target them for degradation. Luo, et al.

Prolyl hydroxylase domain (PHD) proteins, including PHD1, PHD2, and PHD3, mediate oxygen-dependent degradation of hypoxia-inducible factor (HIF) alpha subunits. Suppression of PHD enzymes leads to stabilization of HIFs and offers a potential treatment option for many ischemic disorders, such as peripheral artery occlusive disease, myocardial infarction, and stroke (1).