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. Author manuscript; available in PMC: 2016 Nov 1.
Published in final edited form as: Free Radic Biol Med. 2015 Jun 27;88(0 0):108–146. doi: 10.1016/j.freeradbiomed.2015.06.021

Fig. 14.

Fig. 14

Somatic mutations that upregulate Nrf2. Mutations that result in gain of function are depicted in octagonal shapes outlined in blue, and those that result in loss of function are outlined in red. (A) Transcription of the NFE2L2 gene is increased by mutant KRAS and Myc. (B) Inhibition of GSK-3 and failure to form the DSGIS phosphodegron is likely to occur from mutations in EGFR, PIK3CA and PTEN. (C) Mutations in Keap1 or mutations in the DLG or ETGE motifs in Nrf2 result in failure of CRLKeap1 to ubiquitylate and repress Nrf2. (D) Accumulation of Nrf2 in tumors induces ARE genes, leading to increases in ROS scavenging, increases in metabolic detoxication, and efflux of endogenous electrophiles.