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Future studies demonstrated that KEAP1 does not passively sequester NRF2 in the cytosol, but actively functions as a ubiquitin ligase, leading to ubiquitination and proteasomal degradation of NRF2 (Zhang and Hannink, 2003)

MarchesiniGBugianesiEForlaniGCerrelliFLenziMManiniRet al

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Proc Natl Acad Sci USA 2004

This biochemical transformation, however, comes at an energetic cost ( Specifically, the conversion process requires a significant amount of NADPH, a crucial cofactor that primarily originates from the cytoplasmic glucose-pentose phosphate pathway