Date of Award

2016

Document Type

Open Access Thesis

Department

Chemistry and Biochemistry

Sub-Department

College of Arts and Sciences

First Advisor

Caryn Outten

Abstract

Iron is essential for nearly all life on earth. Cells must maintain sufficient levels of this important nutrient due its function as a central co-factor for many cellular processes. Although iron is extremely plentiful, its poor solubility requires specialized import. On the other side, too much iron inside the cell can lead to the generation of reactive oxygen species (ROS), which have deleterious effects on many cellular functions and have been implicated in a wide variety of diseases such as cancer and Alzheimer’s disease. Using the model eukaryote Saccharomyces cerevisiae, or budding yeast, our research group has accomplished much in determining the mechanism of regulation for the low iron-sensing transcription factor, Activator of Ferrous Transport (Aft1), and its paralog Aft2. However, much remains unknown about the mechanism of regulation for the high ironsensing transcription factor, yeast-activating protein 5 (Yap5). Recent studies in our lab have shown that Yap5, much like Aft1/2, senses iron availability through iron sulfur (Fe- S) cluster binding. Utilizing analytical gel filtration, UV-visible, and CD spectroscopy we have shown that Yap5 and Aft2 interact in vitro and that this interaction is bridged by an iron sulfur cluster transfer. Moreover the transfer has directionality with cluster going from Aft2 to Yap5. This finding is not without physiological repercussions, providing first time evidence that the signal from low to high iron is shared between the two transcriptional regulators and they directly interact with an iron sulfur cluster being a switch in the regulatory response.

Rights

© 2016, John S Hepburn

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