Download Selective Zinc Finger Protein Oxidation and Arsenic Carcinogenesis

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.
.