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USP8 deubiquitinates EPG5. 11 / 12
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"USP8 maintains embryonic stem cell stemness via deubiquitination of EPG5."
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"We propose that deubiquitination of EPG5 by USP8 guards the autophagic flux in ESCs to maintain their stemness."
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"USP8 deubiquitinates EPG5 by removing K63-ubiquitin chains."
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"To test whether USP8 deubiquitinates EPG5, we examined the ubiquitination levels in either Usp8-overexpression or Usp8 ESCs."
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"When we overexpressed Usp8 in ESCs, the ubiquitin modification of EPG5 decreased, while reduced Usp8 expression increased EPG5 ubiquitination (Fig. 5a, b)."
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"These data indicate that USP8 deubiquitinates EPG5."
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"USP8 directly deubiquitinates EPG5 by removing K63-linked ubiquitin and enhance the interaction between LC3 and EPG548.In LUAD, USP8 stabilizes receptor tyrosine kinases (RTKs), contributes to proliferative activity, and inhibits apoptosis in A549 cells49, 50."
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"USP8 regulates ESC identity through deubiquitinating EPG5."
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"Since USP8 directly deubiquitinates EPG5 at K252, we next investigated whether deubiquitination of EPG5 by USP8 impairs the interactions between EPG5 and LC3 and eventually affects ESC stemness."
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"We revealed that the deubiquitinase USP8 maintains ESC identity by directly deubiquitinating EPG5 to consolidate the interaction between EPG5 and LC3 and sustain the normal autophagic flux for stemness maintenance (Fig. 6g)."
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"These data suggested EPG5 is degraded through autophagy in ESCs.In conclusion, we defined a novel mechanism, involving USP8 deubiquitination of EPG5, which underlies autophagy regulation in ESCs."
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