IndraLab

Statements

USP15 decreases the amount of NFE2L2. 7 / 7
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"USP15 inhibits Nrf2 protein levels and expression of its target genes."
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"Taken together these results demonstrate the mechanism by which USP15 leads to decreased Nrf2 protein levels : USP15 is able to stabilize the Cul3-Keap1-E3 ligase complex through deubiquitination of Keap1, resulting in increased E3 ligase activity and ubiquitination of Nrf2, which ultimately leads to degradation of the Nrf2 protein."
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"These results indicate that USP15 may inhibit Nrf2 protein expression and thus, its activity, by increasing Nrf2 protein degradation."
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"We found that USP15 is unable to inhibit Nrf2 protein levels in the absence of Keap1 (XREF_FIG, lanes 3-4)."
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"Further investigation showed that inhibition of USP15 enhanced the activation of NF-E2-related factor 2 (Nrf2) and expression of Nrf2 target genes in HG-simulated podocytes."
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"In addition, USP15 is unable to inhibit Nrf2 protein levels when the seven lysine residues in the Neh2 domain required for ubiquitination by the Keap1-Cul3-E3 ligase complex are mutated (Nrf2-K7) (XREF_FIG, lanes 3-4), or when the Neh2 domain is deleted (XREF_FIG, lanes 5-6)."
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"Conversely, when the Neh6 domain of Nrf2 is deleted, USP15 is still able to inhibit Nrf2 protein expression (XREF_FIG, lanes 7-8)."
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