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Regulation Of The Subunits Of Hypoxia Inducible Factors By Sprouty2 And Its Impact On Different Biological Processes, Kristin Caroline Hicks
Regulation Of The Subunits Of Hypoxia Inducible Factors By Sprouty2 And Its Impact On Different Biological Processes, Kristin Caroline Hicks
Dissertations
The hypoxia inducible factors (HIF1α, HIF2α, HIF1β) promote transcription of genes that regulate glycolysis and cell survival and growth. Sprouty2 (Spry2) is a modulator of receptor tyrosine kinase signaling and inhibits cell proliferation via different mechanisms. Because of the seemingly opposite actions of the HIF and Spry2 on cellular processes, we hypothesized that Spry2 decreases the protein levels of HIF1α, HIF2α and HIF1β by enhancing the proximity of the HIF subunit to an ubiquitin ligase capable of degrading the subunit. Focusing on HIF1α as a prototypical alpha subunit, in a variety of tumor derived cell lines, Spry2 decreases the protein …