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Cuadrado and colleagues first showed that GSK-3 inhibits NRF2 activity, but the identification of sites in NRF2 that are phosphorylated by GSK-3 was achieved several years later using two-dimensional electrophoresis and mass spectrometry: GSK-3 phosphorylates a group of Ser residues at the level of DSGIS motif in the Neh6 domain of NRF2, and this event represents the signal for the recognition by the adapter protein -TrCP, that targets NRF2 for ubiquitination and proteasomal degradation in a KEAP1-independent manner [150, 151]

(A) In normal physiology, conjugated bilirubin is actively excreted into bile through the multidrug resistanceassociated protein 2 (MRP2) on the canalicular membrane, while bile acids are secreted via the bile salt export pump (BSEP)

Chalayer, E

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