IndraLab

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USP8 activates GPX4. 4 / 4
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"As expected, ectopic expression of USP8 increased the protein abundance of GPX4 (SI Appendix, Fig. S4I)."
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"Since there are two major systems to govern protein homeostasis in cells, namely the proteasome-mediated degradation system and the autophagy-lysosome system (39), we aimed to determine the major system in regulating USP8-mediated GPX4 protein stability."
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"Conversely, inhibition of USP8 by genetic ablation or its pharmacological inhibitor (DUB-IN-2) down-regulates GPX4, sensitizing tumor cells to ferroptosis, retarding tumor growth, and increasing tumor-infiltrating CD8 T cells that potentiates the PD-1/PD-L1 blockade therapy (SI Appendix, Fig. S6 E, Right)."
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"Intriguingly, among the ferroptosis-related proteins we examined, USP8 knockdown dramatically decreased the protein abundance of GPX4 in multiple cancer cell lines (Fig. 4 A and B and SI Appendix, Fig. S4 A and B)."
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