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Publication Detail

Title: Chronic Exposure to Particulate Hexavalent Chromium Alters Cdc20 Protein Localization, Interactions and Expression.

Authors: Karri, Naga D; Xie, Hong; Wise Sr, John Pierce

Published In J Carcinog Mutagen, (2013)

Abstract: Hexavalent chromium [Cr(VI)] compounds are well established human lung carcinogens, but it is unknown how they cause lung cancer in humans. Recent data indicate that Cr(VI) induces chromosome instability in human lung cells, and genomic instability is considered a leading mechanism to explain chromate carcinogenesis. The Spindle Assembly Checkpoint (SAC) is a critical regulator of the metaphase-to-anaphase transition and ensures genome stability by preventing chromosomal missegregation events. Bypass of the SAC can lead to genomic instability, manifested as aneuploidy, which eventually leads to tumor formation and cancer. Recent studies in our laboratory demonstrated that chronic exposure to zinc chromate induces SAC bypass in a concentration- and time-dependent manner in human lung fibroblasts. To further study these events, we focused on the cell division cycle 20 (Cdc20) protein, a downstream effector protein in the SAC. Cdc20 has not been studied after Cr(VI) exposure, but other studies show that experimentally induced alterations of Cdc20 localization to kinetochores or of Cdc20 protein expression leads to aneuploidy. Here, we investigated the effects of zinc chromate, a particulate Cr(VI) compound, on Cdc20 localization, protein expression and interactions. Our data show Cdc20 is a target for particulate Cr(VI). Chronic zinc chromate exposure altered Cdc20 kinetochore localization and reduced the interaction of phosphorylated Cdc20 with Mad2, which may underlie zinc chromate-induced SAC bypass.

PubMed ID: 33312751 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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