Arsenite Binds to ZNF598 to Perturb Ribosome-Associated Protein Quality Control.
Lok Ming TamJi JiangPengcheng WangYinsheng WangPublished in: Chemical research in toxicology (2020)
Arsenic pollution in drinking water is a widespread public health problem, and it affects approximately 200 million people in over 70 countries. Many human diseases, including neurodegenerative disorders, are engendered by the malfunction of proteins involved in important biological processes and are elicited by protein misfolding and/or loss of protein quality control during translation. Arsenic exposure results in proteotoxic stress, though the detailed molecular mechanisms remain poorly understood. Here, we showed that arsenite interacts with ZNF598 protein in cells and exposure of human skin fibroblasts to arsenite results in significant decreases in the ubiquitination levels of lysine residues 138 and 139 in RPS10 and lysine 8 in RPS20, which are regulatory post-translational modifications important in ribosome-associated protein quality control. Furthermore, the arsenite-elicited diminutions in ubiquitinations of RPS10 and RPS20 gave rise to augmented read-through of poly(adenosine)-containing stalling sequences, which was abolished in ZNF598 knockout cells. Together, our study revealed a novel mechanism underlying the arsenic-induced proteostatic stress in human cells.
Keyphrases
- quality control
- drinking water
- health risk assessment
- induced apoptosis
- public health
- heavy metals
- amino acid
- health risk
- cell cycle arrest
- binding protein
- protein protein
- endothelial cells
- risk assessment
- stress induced
- endoplasmic reticulum stress
- signaling pathway
- single cell
- high glucose
- particulate matter
- single molecule
- air pollution
- human health