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USP19 activates NFE2L1. 4 / 4
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"Herein, we found that Nrf1 stability and transactivity are both enhanced by USP19, a ubiquitin-specific protease tail-anchored in the endoplasmic reticulum (ER) through its C-terminal transmembrane domain."
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"Conversely, knockout of USP19 causes significant decreases in the abundance of Nrf1 and the entrance of its active isoform into the nucleus, which result in the downregulation of its target proteasomal subunits and a modest reduction in USP19 -/- -derived tumor growth in xenograft mice when compared with wild-type controls."
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"Notably, our recent work further unraveled that the deubiquitinating enzyme USP19 enables activation of its co-localized NFE2L1 in proximity to the ER and, in turn, NFE2L1 in close cooperation with NFE2L2/Nrf2 can tightly govern the transcriptional expression of USP19 and other DUBs insomuch as to form a positive feedback regulatory circuit [49]."
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"Also, USP19 activates NRF1 (encoded by Nfe2l1), thereby altering glucose deprivation sensing, cholesterol abundance, proteasomal inhibition and oxidative stress [122]."
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