The Keap1-Nrf2-antioxidant response element pathway: A review of its regulation by melatonin and the proteasome

- Both melatonin and proteasome inhibitors upregulate antioxidant enzymes.
- The antioxidant action of both melatonin and proteasome inhibitors is mediated by the Nrf2/ARE transcription complex.
- Current data support the hypothesis that the ability of melatonin to modulate antioxidant enzymes is mediated by the proteasome.
- The prediction is made that melatonin will upregulate any antioxidant enzymes that are transcribed in response to an Nrf2/ARE signal.
- The ligase complex that ubiquitinates Nrf2 (Keap1 Cul3-Rbx1) also ubiquitinates IkB kinase and the antiapoptotic factor Bcl-2.