IndraLab

Statements

USP30 inhibits PRKN. 18 / 22
| 18
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"Parkin mediated effects are further regulated by de-ubiquitinating enzymes, such as USP30 and USP35, which reportedly de-ubiquitinate Parkin substrates to antagonize mitophagy [24 *] or Parkin depende[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
26896558
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"The regulation of USP30 activity is important, since hyperactivation of USP30 prevents Parkin from promoting removal of dysfunctional mitochondria (186, 187)."
34391779
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"Our findings provided further verification explaining the functions of Parkin and USP30 in mitophagy and cell senescence, demonstrating that USP30 knockdown could alleviate d-gal-induced mitochondrial damage, and d-gal-promoted myocardial cell senescence by increasing the activity of Parkin.In conclusion, the findings of the present study demonstrated that silencing USP30 upregulated Parkin, resulting in the stimulation of mitophagy and deceleration of myocardial cell senescence (Fig. 6)."
34290230
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"In contrast, a recent report demonstrated that in Drosophila the age dependent increase in mitophagy in both muscle and dopaminergic neurons is dependent on PINK1 and Parkin, and the knockdown of USP15 and USP30 rescues mitophagy in Parkin deficient organisms."
31972372
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"The E3 ligase Parkin ubiquitinates the membrane proteins on targeted mitochondria to initiate mitophagy, whereas USP30 antagonizes Parkin-dependent mitophagy by removing ubiquitin from Parkin substrates."
35250566
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"On one hand, overexpression of USP30 can block Parkin dependent accumulation of Ub chains on MOM proteins in response to depolarization, suggesting that USP30 directly antagonizes Parkin activity."
32142685
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"Strikingly USP30 knockdown invivo could rescue the PINK1 or Parkin -/- phenotypes in Drosophila, indicating that the inhibition of USP30 could be therapeutically advantageous in patients with equivalent null mutations in these genes [XREF_BIBR]."
25345844
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"Emerging promising molecules include selective inhibitor of the mitochondrial deubiquitinase, USP30 that negatively regulates PRKN-mediated mitophagy [132,200]."
| PMC
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"In this regard, USP15 and USP30 were found to antagonize Parkin activity by competing for the common substrates on OMM."
32850842
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"Parkin mediated effects are further regulated by de-ubiquitinating enzymes, such as USP30 and USP35, which reportedly de-ubiquitinate Parkin substrates to antagonize mitophagy [XREF_BIBR] or Parkin dependent cell death [XREF_BIBR]."
26896558
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"However, whether USP30 also comprises specificity at the level of primary ubiquitylation sites in MOM substrates, and the extent to which USP30 activity suppresses the PARKIN feed-forward activation mechanism via pS65-Ub has not been examined in more physiological systems such as neurons."
32142685
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"However, USP30 overexpression antagonizes the activity of Parkin to sustain AKT/mTOR activity and inhibit apoptosis."
35250566
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"The overexpression of USP30 has been reported to inhibit the recruitment of Parkin to damaged mitochondria [11]."
34290230
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"USP30, a transmembrane DUB localized on the mitochondrial outer membrane, antagonizes the function of Parkin by removal of ubiquitin chains from mitochondria [80]."
31630678
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"The best evidence to date comes from analyzing USP30 which appears to antagonize Parkin function as evidenced by the fact that genetic inhibition of USP30 rescues Parkin deficient flies."
26942670
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"In cell systems that have been designed to overexpress Parkin, USP30 can restrict Parkin-dependent ubiquitylation of certain substrates and depolarization-induced mitophagy [76]."
35406655
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"The OMM localized DUB ubiquitin specific processing proteases USP30 and USP15 antagonize PARKIN activity by cleaving ubiquitin chains on mitochondria."
28512624
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"Recent evidence suggests that the mitochondrial deubiquitinase USP30 negatively regulates Parkin mediated mitophagy, providing opportunities to identify USP30 inhibitors and test for their effects in augmenting mitophagy."
33890401