Selective Interaction of Arsenic with Zinc Finger Proteins: Implications and Health Effects

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Environmental or occupational exposure to arsenic may result in the development of cancer and other diseases. Recent research has established that environmentally relevant concentrations of arsenic can disrupt the function of certain zinc finger proteins, which represents an important underlying molecular mechanism for arsenic-induced health effects. In this presentation, we will demonstrate that trivalent arsenite selectively interacts with zinc finger motif of proteins with ≥ 3 cysteine residues, using as examples three specific zinc finger proteins that play critical role in human health and therapeutic intervention: a) Arsenite interacts with key DNA repair proteins XPA and PARP-1, resulting in modification of protein structure and function, leading to accumulation of UV-induced DNA damage and enhanced mutation, thus highlighting how arsenic acts as a potent carcinogen and co-carcinogen to other environmental factors; b) Arsenic selectively inhibits erythropoiesis through the disruption of zinc finger motifs of the transcription factor GATA-1, resulting in anemia and an imbalance of hematopoietic differentiation; and c) Arsenic inhibits tumor cell migration and invasion by interacting with cytoplasmic linker protein 170, a zinc finger protein controlling microtubule dynamics, demonstrating microtubules as a promising anti-metastasis strategy by arsenic against tumor spread and recurrence. Together, these findings highlight the molecular understanding of how low, non-cytotoxic concentrations of arsenic can selectively interact with certain zinc finger proteins, impacting human health.

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Please contact the Grand Round coordinator listed below:

Nancy Strein
Department: Pathology
Phone: (631) 444-3000
Email: nancy.strein@stonybrookmedicine.edu