Selective Sensitization of Zinc Finger Protein Oxidation by ROS Through Arsenic Binding [DNA and Chromosomes]

June 10th, 2015 by Zhou, X., Cooper, K. L., Sun, X., Liu, K. J., Hudson, L. G.

Cysteine oxidation induced by reactive oxygen species (ROS) on redox sensitive targets such as zinc finger proteins plays a critical role in redox signaling and subsequent biological outcomes. We find that arsenic exposure leads to oxidation of certain zinc finger proteins based on arsenic interaction with zinc finger motifs. Analysis of zinc finger proteins isolated from arsenic-exposed cells and zinc finger peptides by mass spectrometry demonstrates preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic are not oxidized by arsenic-generated ROS in the cellular environment. The findings suggest that selectivity in arsenic binding to zinc fingers with three or more cysteines defines the target proteins for oxidation by ROS. This represents a novel mechanism of selective protein oxidation, and demonstrates how an environmental factor may sensitize certain target proteins for oxidation, thus altering the oxidation profile and redox regulation.