title: Selective Sensitization of Zinc Finger Protein Oxidation by Reactive Oxygen Species through Arsenic Binding.
abstract: 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 found that arsenic exposure led 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 demonstrated preferential oxidation of C3H1 and C4 zinc finger configurations. C2H2 zinc finger proteins that do not bind arsenic were 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.
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
authors.forename: Xixi
authors.initials: X
authors.lastname: Zhou
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Cooper
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
authors.forename: Xi
authors.initials: X
authors.lastname: Sun
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131 kliu@salud.unm.edu.
authors.forename: Ke J
authors.initials: KJ
authors.lastname: Liu
authors.affiliation: From the Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131 lhudson@salud.unm.edu.
authors.forename: Laurie G
authors.initials: LG
authors.lastname: Hudson
mesh_terms: D001151:Arsenic / Q000737:chemistry* / Q000633:toxicity; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D003545:Cysteine; D001151:Arsenic
keywords: DNA repair; metal ion-protein interaction; oxidation-reduction (redox); reactive oxygen species (ROS); zinc finger