NIH R01 · 2024
Redox and Protein Homeostasis in Arsenic Tumorigenicity
PROJECT SUMMARY Arsenic is classified as a human carcinogen that has been associated with increased risk of developing cancers of the lung, skin, and bladder. However, the mechanism of arsenic tumorgenicity remains incompletely described. Arsenic has been shown to upregulate NRF2, the master regulator of the cellular stress response in vitro and in vivo. Under non-stress conditions, the basal level of NRF2 is kept low by KEAP1-CUL3-RBX1- mediated ubiquitylation and subsequent 26S proteasomal degradation. During canonical NRF2 activation KEAP1-Cys151 is modified, preventing NRF2 ubiquitylation and increasing the level of NRF2 and its downstream genes to protect cells from environmental…
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