A yeast three-hybrid system that reconstitutes mammalian hypoxia inducible factor regulatory machinery.

BMC Cell Biology
Maria L Alcaide-GermanLuis del Peso

Abstract

Several human pathologies, including neoplasia and ischemic cardiovascular diseases, course with an unbalance between oxygen supply and demand (hypoxia). Cells within hypoxic regions respond with the induction of a specific genetic program, under the control of the Hypoxia Inducible Factor (HIF), that mediates their adaptation to the lack of oxygen. The activity of HIF is mainly regulated by the EGL-nine homolog (EGLN) enzymes that hydroxylate the alpha subunit of this transcription factor in an oxygen-dependent reaction. Hydroxylated HIF is then recognized and ubiquitinilated by the product of the tumor suppressor gene, pVHL, leading to its proteosomal degradation. Under hypoxia, the hydroxylation of HIF by the EGLNs is compromised due to the lack of oxygen, which is a reaction cosubstrate. Thus, HIF escapes degradation and drives the transcription of its target genes. Since the progression of the aforementioned pathologies might be influenced by activation of HIF-target genes, development of small molecules with the ability to interfere with the HIF-regulatory machinery is of great interest. Herein we describe a yeast three-hybrid system that reconstitutes mammalian HIF regulation by the EGLNs and VHL. In this system, yeast g...Continue Reading

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Citations

Nov 5, 2014·Biochemistry. Biokhimii︠a︡·T A TrendelevaR A Zvyagilskaya
Oct 18, 2011·Bioengineered Bugs·Susan Dwane, Patrick A Kiely

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Methods Mentioned

BETA
ubiquitination
three-hybrid
two-hybrid
PCR
two hybrid

Software Mentioned

GraphPad

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