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]
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When administered by qualified healthcare professionals, in a controlled clinical environment, IV vitamin therapy is perfectly safe
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