The oncogenic action of NRF2 depends on de-glycation by Fructosamine-3-kinase (FN3K)

We show that NRF2 activation drives hepatocellular carcinoma development in vivo. Moreover, NRF2 undergoes glucose dependent modification called glycation and requires the de-glycating enzyme FN3K to maintain NRF2' oncogenic functions. Overall design: Gene expression analysis in MYC-driven murine HCC with and without NRF2 activation. NRF2 is activated by targeting its negative regulators Keap1 or Cul3 or targeting NRF2 ETGE motif by sgRNA/Cas9 editing.

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Sanghvi VR, Leibold J, Mina M, Mohan P, Berishaj M, Li Z, Miele MM, Lailler N, Zhao C, de Stanchina E, Viale A, Akkari L, Lowe SW, Ciriello G, Hendrickson RC, Wendel HG