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Integrated model for the regulation of RRM2 protein levels by the mTORC1/2, ATR-CHK1, and WEE1 pathways. In previous work, we found that the inhibition of ATR-CHK1-WEE1 signaling enhances the CDK-mediated degradation of RRM2 (13). In the current work, we showed that the inhibition of mTORC1/2 blocks the synthesis of the RRM2 protein via the activation of 4E-BP1.
