HIF-2 alpha, Tumor Suppression and Cell Survival

Wed, 11/20/2013 - 10:12

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. were able to show with HIF-2 alpha antibody that a C-terminus novel variant of the typical bipartite-type nuclear localization signal (NLS) drove the nuclear accumulation of HIF-2 through an ubquitin-proteasome independent mechanism (1). This NLS is found and conserved in the other HIF family members (HIF-1 and HIF-3) as well. The tumor suppressor gene von Hippel Lindau (VHL) destabilizes HIF-1 and HIF-2, and expression studies with HIF-2 alpha antibody and the Nox oxidase pathway inhibitor diphenyleneiodonium (DPI) suggest that VHL exerts its actions through targeted downregulation of HIF-2 and reactive oxygen species (2).

Western Blot: HIF-2 alpha Antibody Western Blot: HIF-2 alpha Antibody


One group of researchers has interestingly found the stimulation of HIF by a completely different mechanism – that of nerve growth factor (NGF) in rat pheochromocytoma PC12 cells (3). Stimulation was by a completely novel and different mechanism as the HIF-2 alpha antibody was used to show that regulation was hydroxylation-independent and differentially affected HIF-2 alpha but not HIF-1 alpha. Khatua’s group at the Children’s Research Institute performed expression profiling that included the HIF-2 alpha antibody (4). They profiled 133 angiogenesis-related genes in childhood high-grade astrocytoma (HGA) samples searching for potential new therapeutic targets, and found 21 promising markers of which 9 (43%) were EGFR/FKBP12/HIF-2 alpha pathway-associated genes. Recent studies with HIF-2 alpha antibody in cortical astrocytes indicate that EPO expression is mediated by HIF-2 alpha in a paracrine-driven mechanism of neuronal survival (5).

  1. PMID: 11313887
  2. PMID: 17200123
  3. PMID: 12805361
  4. PMID: 12702575
  5. PMID: 16971531

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