USP30 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 30
HGNC Gene Symbol
USP30
Identifiers
hgnc:20065 NCBIGene:84749 uniprot:Q70CQ3
Orthologs
mgi:2140991 rgd:1307949
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP30
Number of Papers
76 retrieved on 2022-05-22

DepMap Analysis

The Dependency Map (DepMap) is a genome-wide pooled CRISPR-Cas9 knockout proliferation screen conducted in more than 700 cancer cell lines spanning many different tumor lineages. Each cell line in the DepMap contains a unique barcode, and each gene knockout is assigned a “dependency score” on a per cell-line basis which quantifies the rate of CRISPR-Cas9 guide drop. It has been found that proteins with similar DepMap scores across cell lines, a phenomenon known as co-dependent genes, have closely related biological functions. This can include activity in the same or parallel pathways or membership in the same protein complex or the same pathway.

We identified the strongest seven co-dependent genes (“Symbol”) for DUBs and ran GO enrichment analysis. We used Biogrid, IntAct, and Pathway Commons PPIDs, and the NURSA protein-protein interaction databases (PPIDs) to determine whether co-dependent genes interact with one another. The “Evidence” column contains the PPIDs in which the interaction appears as well as whether there is support for the association by an INDRA statement. As another approach to identify potential interactors, we looked at proteomics data from the Broad Institute's Cancer Cell Line Encyclopedia (CCLE) for proteins whose expression across ~375 cell lines strongly correlated with the abundance of each DUB; it has previously been observed that proteins in the same complex are frequently significantly co-expressed. The correlations and associated p-values in the CCLE proteomics dataset are provided. And, we determined whether co-dependent genes yield similar transcriptomic signatures in the Broad Institute's Connectivity Map (CMap). A CMap score greater than 90 is considered significantly similar.

DepMap Correlations

Symbol Name DepMap Correlation Evidence CCLE Correlation CCLE Z-score CCLE p-value (adj) CCLE Significant CMAP Score CMAP Type
OAS2 2'-5'-oligoadenylate synthetase 2 0.224 0.12 0.59 7.12e-02
TMEM132D transmembrane protein 132D 0.217
TMEM116 transmembrane protein 116 0.203
GYS2 glycogen synthase 2 -0.198
AOAH acyloxyacyl hydrolase -0.196
KDM1A lysine demethylase 1A 0.195 -0.03 -0.27 6.82e-01
FAM172A family with sequence similarity 172 member A 0.193 0.10 0.46 1.54e-01

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP30using the terms from Gene Ontology and gene sets derived from the Gene Ontology Annotations database via MSigDB.

Using the biological processes and other Gene Ontology terms from well characterized DUBs as a positive control, several gene set enrichment analyses were considered. Threshold-less methods like GSEA had relatively poor results. Over-representation analysis with a threshold of of the top 7 highest absolute value Dependency Map correlations yielded the best results and is reported below.

GO Identifier GO Name GO Type p-value p-value (adj.) q-value

Transcriptomics

The following table shows the significantly differentially expressed genes after knocking out USP30 using CRISPR-Cas9.

Knockout Differential Expression

Symbol Name log2-fold-change p-value p-value (adj.)
RPL22 ribosomal protein L22 6.47e-01 4.79e-07 1.06e-02
PSMB1 proteasome 20S subunit beta 1 3.40e-01 3.72e-06 4.11e-02
RPL19 ribosomal protein L19 2.78e-01 5.59e-06 4.11e-02

Gene Set Enrichment Analysis

There were too few differentially expressed genes to run a meaningful GSEA.

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP30 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP30 deubiquitinates MFN2. 1 / 1
|

ubibrowser
USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2.
USP30 deubiquitinates MFN1. 1 / 1
|

ubibrowser
USP30, a mitochondrial deubiquitinase, promotes mitochondrial fusion by mediating the deubiquitination of ubiquitylated forms of mitofusins, such as Mfn1 and Mfn2.
USP30 deubiquitinates DNM1L. 1 / 1
| 1

reach
Mechanistically, GNPAT recruited the enzyme USP30, which deubiquitylated and stabilized dynamin related protein 1 (DRP1), thereby facilitating regulation of mitochondrial morphology, lipid metabolism, and hepatocarcinogenesis.
USP30 deubiquitinates PRKN. 1 / 1
| 1

reach
Reciprocally, the dequbiquitination enzymes USP30 and USP35 have been shown to antagonize the mitophagy process by deubiquitinating Parkin [138,139].
USP30 deubiquitinates VDAC1. 1 / 1
|

ubibrowser
Review
USP30 deubiquitinates MARCHF5. 1 / 1
| 1

reach
We wanted to test whether USP30 could deubiquitylate MITOL mediated ubiquitylation on PolgammaA.
USP30 deubiquitinates RHOT1. 1 / 1
|

ubibrowser
No evidence text available
USP30 deubiquitinates TOMM70. 1 / 1
|

ubibrowser
Similar findings were reported for another DUB: USP30. USP30 overexpression impaired PARKIN-mediated mitophagy by deubiquitinating mitochondrial substrates that include TOM20, TOM70, and the VDACs
USP30 deubiquitinates NLRP3. 1 / 1
| 1

reach
Mechanistically, we demonstrate that USP30 activates the NLRP3 inflammasome by deubiquitinating NLRP3.
Modified USP30 leads to the deubiquitination of TOMM20. 1 / 1
| 1

reach
As expected, expression of WT USP30, but not a catalytically inactive mutant (C77A), reversed TOMM20 ubiquitylation, but did not affect MFN2 or CISD1 ubiquitylation (XREF_FIG, XREF_SUPPLEMENTARY).
USP30 deubiquitinates TOMM20. 1 / 1
|

ubibrowser
Review

Other Statements

psp cbn pc bel_lc signor biogrid lincs_drug tas hprd trrust ctd vhn pe drugbank omnipath conib crog dgi | rlimsp isi tees geneways eidos trips medscan sparser reach
USP30 affects PRKN
| 19
USP30 inhibits PRKN.
| 13
USP30 inhibits PRKN. 10 / 15
| 11

reach
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]

reach
In this regard, USP15 and USP30 were found to antagonize Parkin activity by competing for the common substrates on OMM.

reach
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].

reach
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.

reach
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.

reach
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.

reach
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.

reach
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].

reach
The OMM localized DUB ubiquitin specific processing proteases USP30 and USP15 antagonize PARKIN activity by cleaving ubiquitin chains on mitochondria.

reach
Emerging promising molecules include selective inhibitor of the mitochondrial deubiquitinase, USP30 that negatively regulates PRKN-mediated mitophagy [132,200].
| PMC
USP30 inhibits mutated PRKN. 2 / 2
| 2

reach
In addition, loss of USP30 can promote the activity of mutant Parkin alleles.

reach
Early studies on USP30 focused on reversal of Parkin dependent MOM ubiquitylation in HeLa cells overexpressing Parkin, as well as in Drosophila, where reduction in USP30 function enhanced the activity of Parkin mutants.
USP30 activates PRKN.
| 6
USP30 activates PRKN. 6 / 6
| 6

reach
USP30 knockdown also increases the ubiquitination level on multiple Parkin substrates, thus confirming that USP30 antagonizes Parkin function.

reach
Although SILAC provides a rigorous way for performing quantification, other studies used label-free quantification to examine targeted mitochondrial outer membrane ubiquitylation by PARKIN in the pres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Although SILAC provides a rigorous way for performing quantification, other studies used label-free quantification to examine targeted mitochondrial outer membrane ubiquitylation by PARKIN in the presence or absence of the mitochondrial deubiquitylating enzyme USP30, leading to the identification of a dozen mitochondrial PARKIN targets that are regulated by USP30 (see below).

reach
Knockdown of the Drosophila homologs of USP15 (CG8334, hereafter called dUSP15) and USP30 (CG3016, hereafter dUSP30) largely rescues the mitochondrial defects of parkin deficient fly muscle in vivo.

reach
Knockdown of the mitochondrial deubiquitinase, USP30, rescues mitophagy defects and disease in flies with pathogenic mutations in Parkin, suggesting a potential role for the inhibition of DUBs that target selective autophagy E3 ligases in the treatment of Parkinson 's and other diseases.

reach
Knockdown of USP30 rescues the defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or PINK1 deficient flies.
USP30 affects cell death
| 5
USP30 inhibits cell death.
| 4
| 4

reach
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]

reach
In contrast, direct siRNA mediated depletion of MIRO2 to comparable residual levels marginally decreased PARP cleavage, whilst a combined knockdown of USP30 and MIRO2 promoted cell death in a similar fashion to USP30 siRNA on its own (XREF_SUPPLEMENTARY).

reach
In addition, overexpressing USP30, a mitochondrial deubiquitinase, attenuated cell death induced by Rot, but not by DA treated cells.

reach
USP30 deubiquitylates mitochondrial Parkin substrates and restricts apoptotic cell death.
USP30 activates cell death.
| 1
| 1

reach
Cell death promoted by USP30 depletion upon treatment with ABT-737 was partially suppressed by BAX knockdown but required concomitant depletion of both BAK and BAX for full suppression (Fig XREF_FIG D and E).
USP30 affects PINK1
| 5
USP30 inhibits PINK1.
| 4
USP30 inhibits PINK1. 4 / 4
| 4

reach
Our data showing that USP30 suppresses a PINK1 dependent component of basal mitophagy indicate a link between USP30 function and phospho-ubiquitin, the key substrate of PINK1 in mitophagy.

reach
One model consistent with this observation envisages that by suppressing basal ubiquitylation at mitochondria, USP30 may effectively limit PINK1 ubiquitin-substrate availability and the generation of pUb ' Parkin-receptor sites ', thus primarily influencing the initiation phase of mitophagy 86.

reach
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].

reach
Here we report that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase PINK1, which are encoded by two genes associated with Parkinson 's disease.
USP30 activates PINK1.
| 1
USP30 activates PINK1. 1 / 1
| 1

reach
Knockdown of USP30 rescues the defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or PINK1 deficient flies.
PRKN affects USP30
| 5
PRKN activates USP30.
| 3
PRKN activates USP30. 3 / 3
| 3

reach
Although SILAC provides a rigorous way for performing quantification, other studies used label-free quantification to examine targeted mitochondrial outer membrane ubiquitylation by PARKIN in the presence or absence of the mitochondrial deubiquitylating enzyme USP30, leading to the identification of a dozen mitochondrial PARKIN targets that are regulated by USP30 (see below).

reach
Although SILAC provides a rigorous way for performing quantification, other studies used label-free quantification to examine targeted mitochondrial outer membrane ubiquitylation by PARKIN in the pres[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Whilst the phosphatase that dephosphorylates p-Ub remains unknown, two DUBs have been identified that deubiquitylate Parkin directed substrates, USP30 and USP15, and USP8 has also been reported to reverse Parkin autoubiquitylation.
PRKN inhibits USP30.
| 2
PRKN inhibits USP30. 2 / 2
| 2

reach
Bingol and colleagues first reported that USP30 antagonises Parkin mediated mitophagy [XREF_BIBR].

reach
One potential explanation for no effect on the feed-forward process with overt depolarization is that activated Parkin rapidly inactivates USP30 or otherwise outpaces Ub removal by USP30, as previously proposed.
4 |
Valproic acid increases the amount of USP30.
3 |
Valproic acid increases the amount of USP30. 3 / 3
3 |

ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available
Valproic acid decreases the amount of USP30.
1 |
Valproic acid decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
USP30 affects Ubiquitin
| 4
USP30 activates Ubiquitin.
| 3
| 3

reach
Thus, USP30 may enable a dynamic ubiquitin economy that is required for multiple core functions at these organelles, whilst preventing inadvertent engagement of the autophagy machinery.

reach
USP30 mediates the removal of the ubiquitin chains added by Parkin.

reach
The ubiquitin chains targeted by USP30 are similar to the ones Parkin adds to its substrates, suggesting that these two enzymes act as antagonists on shared substrates.
USP30 inhibits Ubiquitin.
| 1
| 1

reach
The OMM localized DUB ubiquitin specific processing proteases USP30 and USP15 antagonize PARKIN activity by cleaving ubiquitin chains on mitochondria.
USP30 affects mitophagy
| 3
| 3

eidos
In contrast , USP30 inhibits mitophagy by opposing parkin-mediated ubiquitination of target proteins .

eidos
The depletion of USP30 increases both pexophagy and mitophagy .

eidos
Importantly , USP30 inhibition enhanced ubiquitin phosphorylation and mitophagy even in the absence of Parkin , placing USP30 upstream of Parkin .
| PMC
USP30 affects PEX2
| 3
USP30 inhibits PEX2. 3 / 3
| 3

reach
Overexpression of USP30 prevents pexophagy during amino acid starvation, by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2 [266, 267].

reach
We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2.

reach
Overexpression of USP30 prevents pexophagy during amino acid starvation, by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2 XREF_BIBR, XREF_BIBR.
| 3
| 3

reach
Overexpression of USP30 prevents pexophagy during amino acid starvation, by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2 XREF_BIBR, XREF_BIBR.

reach
Overexpression of USP30 prevents pexophagy during amino acid starvation, by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2 [266, 267].

reach
We demonstrate that USP30 prevents pexophagy by counteracting the action of the peroxisomal E3 ubiquitin ligase PEX2.
Trisulfur affects USP30
| 3
Trisulfur inhibits USP30.
| 2
| 2

reach
It will be of interest to elucidate if S3 can also abolish the USP30 dependent downregulation of mitophagy in Parkinson 's disease.

reach
The inhibition of USP30 by S3 leads to an increase of non degradative ubiquitination of Mfn1/2, which enhances Mfn1 and Mfn2 activity and promotes mitochondrial fusion.
Trisulfur activates USP30.
| 1
| 1

reach
S3 can target deubiquitinase USP30 in mitochondria, an isopeptidase that regulates mitochondrial morphology by deubiquitination of MFN1 and MFN2.
Paracetamol affects USP30
2 |
Paracetamol decreases the amount of USP30. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
2 |
Cyclosporin A decreases the amount of USP30. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
Bisphenol A affects USP30
2 |
Bisphenol A increases the amount of USP30. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
USP30 increases the amount of reactive oxygen species. 2 / 2
| 2

reach
In this regard, we further observed that co-depletion of STK38 and USP30 was sufficient to fully restore total mitochondrial mass and mitochondrial ROS levels to normal values as observed in control cells.

reach
Even more importantly, depletion of USP30, a major opponent of PINK1 and Parkin mediated mitophagy [XREF_BIBR, XREF_BIBR], partially restored soft agar growth, and fully restored total mitochondrial mass and ROS levels of STK38 depleted Ras transformed cells.
USP30 affects MFN1
| 2
USP30 inhibits MFN1. 2 / 2
| 2

reach
S3 induced inhibition of USP30, a mitochondrial localized deubiquitinase, increased the ubiqutinylation of MFN1 and MFN2 without affecting their protein levels.

reach
For example, based on a phenotypic screening, it was shown that the inhibition of USP30 by the compound 15-oxospiramilactone enhances the activity of USP30 's targets Mfn1 and Mfn2 -- two GTPases anchored at the OMM and essential for tethering adjacent mitochondria -- and promotes mitochondrial fusion, thus contributing to the restoration of the mitochondria network [XREF_BIBR].
2 |
Aflatoxin B1 increases the amount of USP30.
1 |
Aflatoxin B1 increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Aflatoxin B1 decreases the amount of USP30.
1 |
Aflatoxin B1 decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Vinclozolin affects USP30
1 |
Vinclozolin decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Urethane affects USP30
1 |
Urethane decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
Trichostatin A increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Topotecan affects USP30
1 |
Topotecan decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Small interfering RNA increases the amount of USP30. 1 / 1
| 1

sparser
The consequence of USP30 inhibition by these compounds, siRNA knockdown and overexpression of dominant-negative USP30 in the mitophagy pathway in different disease-relevant cellular models was explored.
Pyrrolidine affects USP30
| 1
| 1

reach
Recently, Rusilowicz-Jones et al. reported a N-cyano pyrrolidine derivative (FT3967385) inhibited USP30 with an IC 50 of 1.5 nM and, whilst it showed some off-target inhibition of USP6, enhanced mitophagy in cultured neuroblastoma cells [XREF_BIBR].
Oxaliplatin affects USP30
1 |
Oxaliplatin decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Nickel atom affects USP30
1 |
Nickel atom decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Methyl methanesulfonate increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
Methamphetamine decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-877-5p decreases the amount of USP30. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Hsa-miR-484 affects USP30
1 |
Hsa-miR-484 decreases the amount of USP30. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Ethyl methanesulfonate increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Ethanol affects USP30
| 1
Ethanol activates USP30. 1 / 1
| 1

reach
Quercetin administration markedly attenuated the unfavorable changes of Parkin, Usp30 and VDAC1 induced by ethanol.
Doxorubicin affects USP30
1 |
Doxorubicin decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
Deoxynivalenol increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Decabromodiphenyl ether increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Copper(II) sulfate increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
Benzo[a]pyrene decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Atrazine affects USP30
1 |
Atrazine increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
Abrine affects USP30
1 |
Abrine increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
USP30 affects pexophagy
| 1
| 1

eidos
The depletion of USP30 increases both pexophagy and mitophagy .
USP30 affects pUb
| 1
USP30 inhibits pUb. 1 / 1
| 1

reach
One model consistent with this observation envisages that by suppressing basal ubiquitylation at mitochondria, USP30 may effectively limit PINK1 ubiquitin-substrate availability and the generation of pUb ' Parkin-receptor sites ', thus primarily influencing the initiation phase of mitophagy 86.

reach
In HCCs arising in DEN and CCl 4 -treated mice, USP30 deletion attenuated lipogenesis, inflammation and tumorigenesis irrespective of diet.

reach
Beyond Deubiquitylation : USP30 Mediated Regulation of Mitochondrial Homeostasis.
USP30 affects dopamine
| 1
| 1

reach
RNAi mediated knockdown of USP30 specifically in dopaminergic neurons via the dopamine decarboxylase driver completely rescued the paraquat induced behavioral deficit and prevented dopamine depletion [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP30 affects autophagy
| 1
| 1

reach
The mitochondrial deubiquitylase USP30 negatively regulates the selective autophagy of damaged mitochondria.
| 1

reach
Knockdown of USP30 could induce the mitochondrial apoptosis pathway [XREF_BIBR].
USP30 affects UCHL1
| 1
USP30 activates UCHL1. 1 / 1
| 1

reach
Structure of a USP20 inhibitor from GSK.Figure 29 Structure of a USP30 inhibitor.Structures of UCHL1 inhibitors.VAE(OMe)-FMK Structure of a weak tripeptide FMK UCHL1 inhibitor.Figure 33 Structures of UCHL3 inhibitors.Structures of TRABID and RPN11 inhibitors.
USP30 affects UBD
| 1
USP30 inhibits UBD. 1 / 1
| 1

reach
As expected, Cys and His mutations abrogate USP30 activity, while Ser mutation to Ala, but also to Asn or Asp, that are usually found in USP DUBs XREF_BIBR, reduce activity in both mono- and diubiquitin based substrate cleavage assays (XREF_FIG, XREF_SUPPLEMENTARY).
USP30 affects STK38
| 1
USP30 activates STK38. 1 / 1
| 1

reach
In this regard, we speculated that USP30 depletion might compensate for STK38 deficiency, hence restoring anchorage independent growth of STK38 depleted Ras transformed cells.
USP30 affects MFN2
| 1
USP30 inhibits MFN2. 1 / 1
| 1

reach
S3 induced inhibition of USP30, a mitochondrial localized deubiquitinase, increased the ubiqutinylation of MFN1 and MFN2 without affecting their protein levels.
USP30 affects Death
| 1
USP30 inhibits Death. 1 / 1
| 1

reach
In contrast, a systematic analysis of DUB knockdown phenotypes in Drosophila highlighted a protective role for USP30 during development : even incomplete suppression of USP30 expression caused developmental lethality or early death in adulthood [XREF_BIBR].

eidos
The depletion of USP30 was shown to enhance the degradation of mitochondria in neuronal and HeLa cell cultures [ 106,109 ] .
1 |
Phthalic Acids decreases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
PINK1 affects USP30
| 1
PINK1 activates USP30. 1 / 1
| 1

reach
We further reconstitute USP30 regulatory mechanisms in vitro, and show how even incomplete PINK1 kinase mediated ubiquitin chain phosphorylation impacts USP30 activity.
Niclosamide affects USP30
1 |
Niclosamide increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
MUL1 affects USP30
| 1
MUL1 inhibits USP30. 1 / 1
| 1

reach
We suggest that Usp30 activity is suppressed by the increased levels of Park and Mul1, which restore the correct mitophagy.
MFN1 affects USP30
| 1
MFN1 inhibits USP30. 1 / 1
| 1

reach
Enhancement of MFN1 activity by S3 mediated inhibition of USP30 (mitochondria localized deubiquitinase) restored mitochondrial morphology and ATP levels in fusion deficient mouse embryo fibroblasts (Yue etal., 2014).
Antirheumatic Agents increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available
1 |
(-)-anisomycin increases the amount of USP30. 1 / 1
1 |

ctd
No evidence text available