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Transcript
Selective Zinc Finger Protein Oxidation and Arsenic Carcinogenesis Ke Jian Liu Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131, USA 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. Evidence from our lab and others demonstrates that arsenic inhibits DNA repair at low, non-cytotoxic concentrations and amplifies the mutagenic, genotoxic and carcinogenic impact of other DNA-damaging agents, such as ultraviolet (UV) radiation. Our recent research provides direct evidence that arsenite binding renders C3H1 and C4 zinc finger DNA repair proteins vulnerable to arsenite-generated oxidative stress, thereby linking the proposed mechanisms of oxidative stress and zinc finger disruption. The findings demonstrate that arsenic binding selectivity for C3H1 and C4 zinc fingers confers selective oxidation of cysteine residues within the zinc finger protein targets. We find that arsenite binding to zinc fingers not only leads to loss of zinc, but renders the zinc finger more susceptible to oxidation, resulting in ultimate loss of arsenite as well. 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. .