Aryl hydrocarbon receptor sulfenylation promotes glycogenolysis and rescues cancer chemoresistance.

ABSTRACT: Elevation of reactive oxygen species (ROS) levels is a general consequence of tumor cells' response to treatment and may cause tumor cell death. Mechanisms by which tumor cells clear fatal ROS, thereby rescuing redox balance and entering a chemoresistant state, remain unclear. Here, we show that cysteine sulfenylation by ROS confers on aryl hydrocarbon receptor (AHR) the ability to dissociate from the heat shock protein 90 complex but to bind to the PPP1R3 family member PPP1R3C of the glycogen complex in drug-treated tumor cells, thus activating glycogen phosphorylase to initiate glycogenolysis and the subsequent pentose phosphate pathway, leading to NADPH production for ROS clearance and chemoresistance formation. We found that basic ROS levels were higher in chemoresistant cells than in

SUBMITTER: Zhou N 

PROVIDER: S-EPMC10721154 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature