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USP8 activates autophagy. 11 / 12
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"Moreover, it was demonstrated in vivo that MnS x , on the one hand, mediated the activation of tumor autophagy by USP8 via intracellular H 2 S, while Mn 2+ promoted the maturation of dendritic cells, activated cytotoxic T lymphocytes and contributed to tumor eradication."
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"Thus, important prerequisites for compound optimization and drug development exist for USP8 and can be readily exploited in aged-associated neurodegenerative disease models.In summary, in this work we show that we can enhance autophagy and mitophagy by down-regulating USP8, a DUB that is upregulated in age-related neurodegenerative conditions [19,42]."
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"For example, the ubiquitin-specific peptidase 8 (USP8) inhibitor DUB-IN-1 can inhibit ESCC cell growth by stimulating autophagy through p53-dependent adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) [55]."
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"Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells also affects autophagy which appears to be deregulated with an increased number of autophagosomes and increased autophagy flux."
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"Inactivation of human UBPY in HeLa cells activates autophagy."
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"These data indicate that USP8 guards autophagic flux in ESCs.EPG5 mediates autophagy by direct binding to LC3 using its LIR motif , which is conserved in eukaryotes (Fig. 6e)."
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"We show here that UBPY silencing also activates autophagy in absence of CCCP treatment, which strongly suggests that UBPY is not connected exclusively to mitophagy."
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"In summary, USP8 inhibition has been shown to reduce the autophagy protein p62 during infection with Salmonella, which is correlated with increased autophagy flux.3 Discussion."
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"Interestingly, USP8 also enhances the interaction between EPG5 and LC3 in embryonic stem cells (EPCs), where EPG5 is a novel candidate for regulating autophagy in these cells (Gu et al., 2019); the knockdown of USP8 decreased the autophagy flux, while USP8 overexpression caused an increase in autophagy under normal and starvation conditions (Gu et al., 2019)."
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"We found that USP8 down-regulation enhances autophagy and mitophagy in flies and in neurons of human origin, providing a mechanistic explanation for the protective effect of USP8 reduction observed in several models of neurodegeneration."
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"USP8 Down-Regulation Induces Autophagy in Flies."
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