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Additionally, when activated, the transcription factor, NRF2 binds to the antioxidant response element (ARE) and directs the synthesis of the rate-limiting enzymes responsible for glutathione synthesis: glutamate–cysteine ligase (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM)

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In addition, glutamine uptake can be negatively regulated by retinoblastoma (Rb) tumor suppressor family, whose deletion increases glutamine uptake via the E2F -dependent upregulation of SLC1A5/ASCT2 and GLS1 [22]