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Hypoxia-related proteins display lethal teamwork in supporting malignancy

Hypoxia refers to a pathological condition characterized by an inadequate supply of oxygen to the whole organism or to a specific tissue. Hypoxia-related proteins play an essential role in homeostasis responding to changes in oxygen levels. They also contribute to the physiology of several pathologies such as myocardial and cerebral ischemia, pulmonary hypertension, congenital heart disease, chronic obstructive pulmonary disease and cancer. Over-expression of hypoxia-inducible factors 1 and 2 (HIF-1α and HIF-2α) in solid tumors correlate with the expression of HIF-1α- and HIF-2α-target genes capable of promoting angiogenesis, anaerobic metabolism, and survival/escape mechanism from a hypoxic microenvironment. However, in order to fully activate these target genes, other transcription factors working together with HIF-1α and/or HIF-2α. In their recent publication in Molecular and Cellular Biology, Dr. Pawlus from the Program in Molecular Biology at the University of Colorado labeled RNAs from cancer cell lines using Enzo’s BioArray® High Yield RNA transcript labeling kit for microarray analysis and successfully demonstrated that upstream stimulating factor 2 (USF2) significantly influences the hypoxic induction of several known HIF-2α- but not HIF-1α-target genes. Looking further into this mechanism, USF2 was shown to physically interact with HIF-2α and its co-activators, CBP and P300, and bind to the promoters/enhancers of PAI1 and EPO, two HIF-2α target genes. As a result, USF2 was identified as being a critical player in the driving of HIF-2α-dependent tumorigenesis. However, it remains to be seen whether such interactions exist in normal cells under normoxic or hypoxic conditions.

Enzo Life Sciences offers a comprehensive portfolio for studying hypoxia including live cell analysis kits, gene expression analysis assays, antibodies and biochemicals; some of which are described below:

 


References:

  • Pawlus MR, et al. Upstream stimulatory factor 2 and hypoxia-inducible factor 2a (HIF2a) cooperatively activate HIF2 target genes during hypoxia. Mol. Cell. Biol. (2012) 32: 4595.

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