USP33 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 33
HGNC Gene Symbol
USP33
Identifiers
hgnc:20059 NCBIGene:23032 uniprot:Q8TEY7
Orthologs
mgi:2159711 rgd:1307848
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP33
Number of Papers
63 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
IFI44 interferon induced protein 44 0.288 0.23 1.19 1.48e-02
DNAJB4 DnaJ heat shock protein family (Hsp40) member B4 0.259 0.15 0.74 1.02e-02
NF1 neurofibromin 1 -0.253 0.10 0.47 1.03e-01
TLCD4 TLC domain containing 4 0.252 0.31 1.62 2.82e-06
SAMD13 sterile alpha motif domain containing 13 0.248
PSMB3 proteasome 20S subunit beta 3 -0.245 Reactome (9) -0.00 -0.11 9.64e-01
DNAI3 dynein axonemal intermediate chain 3 0.245

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP33using 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

Literature Mining

INDRA was used to automatically assemble known mechanisms related to USP33 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
USP33 deubiquitinates ARRB2. 7 / 7
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Subsequent deubiquitination of beta-arrestin 2 by the deubiquitinase USP33 dissociates the receptor, beta, and arrestin complex.

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Beta-arrestin-2 can be ubiquitinated by Mdm2 (see above) and deubiquitinated by the DUB enzyme USP33.

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Importantly, a knockdown of USP20 and USP33 enhances beta-arrestin2 ubiquitination and increases beta 2 AR degradation [XREF_BIBR, XREF_BIBR].

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USP33 leads to de-ubiquitination of beta-arrestin2 with non degradative effects.

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Further results verified that USP33 can deubiquitinate beta-arrestin2, subsequently block the internalization of SDF-1-stimulated CXCR4, and disrupt beta-arrestin-dependent ERK activation.

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Given that the enzymatic activity of USP33 is important in regulating CXCR4 internalization, we were interested in whether USP33 can deubiquitinate beta-arrestin2 and subsequently regulate CXCR4 endocytosis.

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No evidence text available
USP33 deubiquitinates ROBO1. 7 / 7
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These results show that USP33 mediates Slit-Robo signaling by deubiquitinating and stabilizing Robo1 in CRC cells (XREF_SUPPLEMENTARY).

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USP33 mediates Slit2 signaling by deubiquitinating and stabilizing Robo1.

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USP33 deubiquitinates ROBO1 in lung cancer cells to maintain its stability, thereby regulating SLIT2 activity and inhibiting cancer cell metastasis [XREF_BIBR].

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Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1.

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USP33 deubiquitinates and stabilizes Robo1.

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Though direct deubiquitination of Robo1 by USP33 has not been reported, it is reasonable to speculate that USP33 deubiquitinates and thus rescues Robo1 from degradation during the Slit response.

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Cell based assays support a model in which USP33 reverses Robo1 ubiquitination : knockdown of USP33 increases levels of ubiquitinated Robo1, while USP33 overexpression reduces ubiquitinated Robo1 levels [XREF_BIBR].
USP33 deubiquitinates CCP110. 3 / 3
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USP33 potently and specifically deubiquitinates CP110, but not other cyclin-F substrates.

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USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110

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Thus, USP33 specifically de-ubiquitylates CP110 in vitro and in vivo, explaining how USP33 stabilizes CP110.
USP33 deubiquitinates RALB. 3 / 3
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Starvation induced deubiquitination of RALB by USP33 (XREF_FIG c) prevents the association with SEC5 and triggers the interaction to another exocyst subunit, EXO84 [XREF_BIBR].

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Review

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Another example in the context of early signaling events is the deubiquitination of RALB by USP33, which enables the interaction of non modified RALB with Beclin 1 complexes in order to induce autophagy.
USP33 leads to the deubiquitination of AR. 2 / 2
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104 Two DUBs USP20 and USP33 have been shown to mediate deubiquitination of beta 2 AR.

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Ubiquitination of the beta 2 AR is reversed by the deubiquitinases USP20 and USP33, which tonically associate with the beta 2 AR.
USP33 deubiquitinates PRKN. 2 / 2
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Cellular and in vitro assays illustrated that USP33 deubiquitinates PRKN in a DUB activity dependent manner.

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USP33 deubiquitinates PRKN and parkin and antagonizes its role in mitophagy.
USP33 deubiquitinates GCGR. 2 / 2
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Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist activated GCGRs at early endosomes.

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Our data suggest that USP33 constitutively deubiquitinates the GCGR, whereas both STAMBP and USP33 deubiquitinate agonist activated GCGRs at early endosomes.
USP33 deubiquitinates MYC. 2 / 2
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USP33, as a deubiquitinating enzyme, could deubiquitinate c-Myc, an important proliferation regulator.

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IP experiments showed that USP33 interacted with c-Myc (XREF_FIG), and USP33 knockdown profoundly enhanced c-Myc ubiquitination (XREF_FIG).
USP33 deubiquitinates TRAF6. 1 / 1
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We report that two ubiquitin specific peptidases, USP20 and USP33, deubiquitinate TRAF6 and suppress IL-1beta-induced NF-kappaB activation.
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USP33 deubiquitinates ubiquitinated VHL. 1 / 1
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Can VDU1 or VDU2 deubiquitinate the ubiquitinated pVHL to salvage it from degradation on certain conditions?
USP33 deubiquitinates RAB40AL. 1 / 1
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It has also been demonstrated that USP33 deubiquitinates RAS like GTPase RALB and therefore promoting autophagosome formation [18].
Modified USP33 leads to the deubiquitination of CCP110. 1 / 1
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Remarkably, USP33 over-expression diminished CP110 ubiquitylation provoked by ectopic production of cyclin F in cells (XREF_FIG).
USP33 deubiquitinates DIO2. 1 / 1
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Ubiquitinated D2 can be either targeted to proteasomal degradation or reactivated by deubiquitination, a process that is mediated by the deubiquitinases USP20/33 and is important in adaptive thermogenesis.
USP33 deubiquitinates Phosphatase. 1 / 1
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USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2 +/Mn2 + dependent 1A), a phosphatase for Smad2/3.
USP33 deubiquitinates SP1. 1 / 1
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USP33 regulates c-Met expression by deubiquitinating SP1 to facilitate metastasis in hepatocellular carcinoma.
USP33 deubiquitinates HIF1A. 1 / 1
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In addition, VDU2, but not VDU1, is able to interact with and deubiquitinate HIF1alpha, and rescue it from proteasome mediated degradation.
USP33 deubiquitinates ADRB2. 1 / 1
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Review
USP33 deubiquitinates PPM1A. 1 / 1
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USP33 could deubiquitinate PPM1A (protein phosphatase, Mg2 +/Mn2 + dependent 1A), a phosphatase for Smad2/3.
Modified USP33 leads to the deubiquitination of ROBO1. 1 / 1
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Overexpression of wild-type USP33, but not catalytically inactive C163A mutant of USP33, decreased the ubiquitination of Robo1.
USP33 deubiquitinates ARRB1. 1 / 1
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We now report the discovery that the deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) binds beta-arrestin2 and leads to the deubiquitination of beta-arrestins.
USP33 deubiquitinates ID2. 1 / 1
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Therefore, we posit that overexpressed USP1 interferes with mesenchymal stem cell differentiation and thereby fosters the development of malignant mesenchymal cell populations.Our screen for DUBs capa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP33 deubiquitinates PRKN on K435. 1 / 1
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USP33 prefers to remove K6, K11, K48 and K63 linked ubiquitin conjugates from PRKN, and deubiquitinates PRKN mainly at Lys435.
USP33 leads to the deubiquitination of DUSP1. 1 / 1
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Mechanistically, we found that USP33 could inhibit the Lys48 (K48)-linked polyubiquitination of DUSP1.
USP33 deubiquitinates ROBO1 on lysine. 1 / 1
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biopax:reactome
No evidence text available

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
BTRC affects USP33
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BTRC activates USP33.
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BTRC activates USP33. 9 / 9
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Consequently, beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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Furthermore, we found that beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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These results indicate that beta-TrCP attenuates USP33 mediated inhibition of cell proliferation.

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Taken together, these results suggest that beta-TrCP downregulates USP33 expression at the protein level but not at the mRNA level.To uncover the mechanism of USP33 downregulation mediated by beta-TrC[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Our results showed that MG132 blocked beta-TrCP-mediated USP33 downregulation, suggesting that beta-TrCP promotes USP33 downregulation via the proteasome pathway.

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Taken together, we found that beta-TrCP attenuates USP33 mediated inhibition of cell proliferation and invasion.So far, the study of USP33 is still very limited.

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The results showed that knockdown of beta-TrCP in cells slowed down the degradation rate of endogenous USP33 and therefore enhanced USP33 protein stability.

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Furthermore, we demonstrated that overexpression of beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and invasion.

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These data suggest that beta-TrCP might mediate USP33 downregulation at the protein level.
BTRC decreases the amount of USP33.
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BTRC decreases the amount of USP33. 3 / 4
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Taken together, these results suggest that beta-TrCP downregulates USP33 expression at the protein level but not at the mRNA level.To uncover the mechanism of USP33 downregulation mediated by beta-TrC[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Here, we found that beta-TrCP downregulated cellular levels of endogenous USP33.

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In contrast, knockdown of beta-TrCP in HEK293T cells upregulated endogenous USP33 protein levels.
BTRC inhibits USP33.
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BTRC inhibits USP33. 3 / 3
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Thus, our data revealed a new regulatory mechanism of the deubiquitinase USP33, and uncovered an additional signaling pathway, that is, beta-TrCP downregulates USP33 to promote cell proliferation.HeLa[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

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Deubiquitinase USP33 is negatively regulated by beta-TrCP through ubiquitin dependent proteolysis.

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The results showed that knockdown of beta-TrCP in cells slowed down the degradation rate of endogenous USP33 and therefore enhanced USP33 protein stability.
BTRC increases the amount of USP33.
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BTRC increases the amount of USP33. 1 / 1
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Conversely, knockdown of beta-TrCP significantly decreased the ubiquitination levels of endogenous USP33.
Modified BTRC increases the amount of USP33. 1 / 1
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We found that overexpression of beta-TrCP did not decrease, but slightly increased USP33 mRNA levels.

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USP33 knockdown significantly upregulated tumor cell proliferation and metastasis.

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USP33 inhibits cell proliferation, migration, and invasion.

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Consequently, beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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These results indicate that beta-TrCP attenuates USP33 mediated inhibition of cell proliferation.

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Furthermore, we found that beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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Cellular studies with TPC-1 and BCPAP cells demonstrated that USP33 can attenuate the cell capacities of proliferation, migration and invasion.

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Our data showed that knockdown of USP33 promoted the proliferation of both HeLa and HCT116 cells.

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Taken together, we found that beta-TrCP attenuates USP33 mediated inhibition of cell proliferation and invasion.So far, the study of USP33 is still very limited.

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Overexpression of USP33 can significantly inhibit cell proliferation, migration, and invasion.

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Furthermore, we demonstrated that overexpression of beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and invasion.

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Moreover, overexpression of USP33 Cys : His can slightly promote cell proliferation and invasion (XREF_SUPPLEMENTARY), instead of the inhibiting effects caused by USP33 wild type.

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Next, functional rescue assays were performed to further verify that the miR-365a-3p-mediated downregulation of USP33 promotes the proliferation, migration, and invasion of lung cancer cells.

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Ubiquitin specific peptidase 33 promotes cell proliferation and reduces apoptosis through regulation of the SP1/PI3K/AKT pathway in retinoblastoma.

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Using HeLa or HCT116 cells as a model, we analyzed the cell proliferation mediated by USP33.

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This is the first evidence for a lung cancer invasion and metastasis mechanism in which miR-365a-3p directly targets and downregulates USP33, which further promotes the proliferation, migration, and invasion activities of lung cancer.

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On the other hand, USP33 knock-down promoted cell proliferation and invasion under SDF-1 stimulation; whereas dynasore (an internalization inhibitor) pretreatment in USP33 silencing cells showed a distinct antipromoting effect, revealing the participation of CXCR4 internalization in regulating tumor progress.
| 1 15

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Cell experiments showed that USP33 overexpression significantly inhibited the proliferation, migration, and invasion of GAC cells.

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Furthermore, we demonstrated that overexpression of beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and invasion.

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Consequently, beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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Cellular studies with TPC-1 and BCPAP cells demonstrated that USP33 can attenuate the cell capacities of proliferation, migration and invasion.

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[USP33 suppresses lung adenocarcinoma lung cell invasion and metastasis by down-regulating SLIT2 and ROBO1 signaling pathway].

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USP33 inhibits cell proliferation, migration, and invasion.

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USP33 silencing can promote the migration, invasion and metastasis of lung adenocarcinoma cells in vitro, and the mechanism may involve IL-6 and SLIT2 and ROBO1 signaling pathways.

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Furthermore, we found that beta-TrCP attenuated USP33 mediated inhibition of cell proliferation and cell invasion.

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Overexpression of USP33 can significantly inhibit cell proliferation, migration, and invasion.
| 1 6

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This is the first evidence for a lung cancer invasion and metastasis mechanism in which miR-365a-3p directly targets and downregulates USP33, which further promotes the proliferation, migration, and invasion activities of lung cancer.

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On the other hand, USP33 knock-down promoted cell proliferation and invasion under SDF-1 stimulation; whereas dynasore (an internalization inhibitor) pretreatment in USP33 silencing cells showed a distinct antipromoting effect, revealing the participation of CXCR4 internalization in regulating tumor progress.

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We found that USP33 knockdown inhibited the invasion and metastasis in HCC cells both in vitro and in vivo, which was partly dependent on c-Met.

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Next, functional rescue assays were performed to further verify that the miR-365a-3p-mediated downregulation of USP33 promotes the proliferation, migration, and invasion of lung cancer cells.

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Our results reveal that USP33 acts as the deubiquitinating enzyme of SP1 and contributes to HCC invasion and metastasis through activation of the SP1 / c-Met axis .

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Moreover, overexpression of USP33 Cys : His can slightly promote cell proliferation and invasion (XREF_SUPPLEMENTARY), instead of the inhibiting effects caused by USP33 wild type.

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Our results reveal that USP33 acts as the deubiquitinating enzyme of SP1 and contributes to HCC invasion and metastasis through activation of the SP1 and c-Met axis.
USP33 affects ROBO1
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USP33 increases the amount of ROBO1.
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USP33 increases the amount of ROBO1. 2 / 2
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Knocking-down USP33 in H1299 cells increased the level of ubiquitinylated Robo1 in the presence of MG132, an inhibitor of the ubiquitin proteasome system.

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USP33 silencing in A549 and SPC-A-1 cells significantly promoted the cell migration, invasion and metastasis and obviously down-regulated the expressions of SLIT2 and ROBO1.
Modified USP33 increases the amount of ubiquitinated ROBO1. 1 / 1
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USP33 knockdown increased the ubiquitinated Robo1 level, whereas overexpression of GFP-USP33 reduced the ubiquitinated Robo1 level (XREF_SUPPLEMENTARY), suggesting that USP33 play a role in Robo1 deubiquitination.
Modified USP33 increases the amount of ROBO1. 1 / 1
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Conversely, overexpression of wild-type USP33, not the C163A mutant USP33, in H1299 cells increased the levels of Robo1.
USP33 inhibits ROBO1.
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USP33 inhibits ROBO1. 2 / 3
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Similarly, the downregulation of USP33 (a ubiquitin ligase enzyme) reduces the stability of the ROBO1 receptor in lung cancer cells 29 and breast cancer cell migration 30.

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Downregulation of USP33 reduces the protein stability of Robo1 in lung cancer cells, providing a previously unknown mechanism for USP33 function in mediating Slit activity in lung cancer cells.
USP33 decreases the amount of ROBO1.
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USP33 decreases the amount of ubiquitinated ROBO1. 2 / 2
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USP33 knockdown increased the ubiquitinated Robo1 level, whereas overexpression of GFP-USP33 reduced the ubiquitinated Robo1 level (XREF_SUPPLEMENTARY), suggesting that USP33 play a role in Robo1 deubiquitination.

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Cell based assays support a model in which USP33 reverses Robo1 ubiquitination : knockdown of USP33 increases levels of ubiquitinated Robo1, while USP33 overexpression reduces ubiquitinated Robo1 levels [XREF_BIBR].
USP33 decreases the amount of ROBO1. 1 / 1
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Overexpression of USP33 reduced, whereas knocking-down USP33 increased the level of ubiquitinylated Robo1 (XREF_FIG).
USP33 activates ROBO1.
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USP33 activates ROBO1. 1 / 2
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Though direct deubiquitination of Robo1 by USP33 has not been reported, it is reasonable to speculate that USP33 deubiquitinates and thus rescues Robo1 from degradation during the Slit response.
USP33 affects CCP110
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USP33 activates CCP110.
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USP33 activates CCP110. 4 / 8
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Further, USP33 suppression significantly reduced CP110 protein half-life from ~ 4.5 hours to ~ 2 hours (XREF_SUPPLEMENTARY).

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We observed that USP33 depletion did not lead to a reduction in RRM2 levels (XREF_SUPPLEMENTARY), indicating that USP33 specifically stabilizes CP110.

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Further, depletion of USP33 in two PDAC cell lines (Panc1 and MiaPaCa2) led to a reduction in CP110 levels (XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY), indicating that USP33 stabilizes CP110 in PDAC cells.

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USP33 promotes the generation of excessive centriolar foci due to elevated levels of CP110 because (1) over-expression of human or murine USP33 led to CP110 up-regulation in multiple cell lines (XREF_SUPPLEMENTARY) and (2) depletion of CP110 overrode USP33 mediated generation of centriolar foci (XREF_SUPPLEMENTARY).
USP33 inhibits CCP110.
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USP33 inhibits CCP110. 1 / 3
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Finally, CDK2 inhibitor response was enhanced when combined with knockdown of the deubiquitinase USP33 that in turn accelerates CP110 protein degradation.
| 1 6
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Our results reveal that USP33 acts as the deubiquitinating enzyme of SP1 and contributes to HCC invasion and metastasis through activation of the SP1 and c-Met axis.

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We found that USP33 knockdown inhibited the invasion and metastasis in HCC cells both in vitro and in vivo, which was partly dependent on c-Met.

eidos
Our results reveal that USP33 acts as the deubiquitinating enzyme of SP1 and contributes to HCC invasion and metastasis through activation of the SP1 / c-Met axis .

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Secondly, the details of mechanisms by which USP33 promotes GAC growth and metastasis are still unclear; for example, the effects of USP33 on cell viability may be caused by either suppressing proliferation or enhancing apoptosis.
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USP33 knockdown significantly upregulated tumor cell proliferation and metastasis.

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USP33 silencing can promote the migration, invasion and metastasis of lung adenocarcinoma cells in vitro, and the mechanism may involve IL-6 and SLIT2 and ROBO1 signaling pathways.

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[USP33 suppresses lung adenocarcinoma lung cell invasion and metastasis by down-regulating SLIT2 and ROBO1 signaling pathway].
USP33 affects CXCR4
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USP33 inhibits CXCR4.
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USP33 inhibits CXCR4. 3 / 5
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We demonstrated that USP33 overexpression can attenuate CXCR4 internalization, while USP33 knock-down showed the opposite effect.

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We also demonstrated that in the LoVo cells transfected with CXCR4, overexpression of beta-arrestin2 can further promote cell proliferation, while co-overexpression of USP33 can attenuate the oncogenetic effects of CXCR4 (XREF_SUPPLEMENTARY).

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On the other hand, we tested the level of total receptors after SDF-1 stimulation and demonstrated that USP33 knock-down can increase the degradation of CXCR4, while USP33 overexpression can inhibit its degradation.
USP33 activates CXCR4.
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USP33 activates CXCR4. 2 / 2
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and silencing USP33 can promote internalization and degradation of CXCR4.

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We have proved that USP33 knock-down can promote the internalization and degradation of CXCR4.
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Valproic acid decreases the amount of USP33.
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Valproic acid decreases the amount of USP33. 3 / 3
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ctd
No evidence text available

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No evidence text available

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No evidence text available
Valproic acid increases the amount of USP33.
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Valproic acid increases the amount of USP33. 1 / 1
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ctd
No evidence text available
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USP33 activates cell migration.
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Expression of the C163A-mutant USP33 abolished Slit suppression of H1299 cell migration, supporting that deubiquitinating activity of USP33 is important in mediating Slit activity in inhibiting lung cancer cell migration.

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For instance, USP33 contributes to Slit-mediated breast cancer cell migration [49].
| PMC
USP33 inhibits cell migration.
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Similarly, the downregulation of USP33 (a ubiquitin ligase enzyme) reduces the stability of the ROBO1 receptor in lung cancer cells 29 and breast cancer cell migration 30.
USP33 affects SLIT2
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USP33 inhibits SLIT2.
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USP33 inhibits SLIT2. 2 / 2
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Enhanced USP33 expression increased Slit2 inhibition of cell migration (XREF_FIG), whereas knocking down USP33 blocked the inhibitory effect of Slit on cell migration (XREF_FIG).

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Ectopic expression of Slit2 significantly reduced the number of lung metastasis sites, and USP33 overexpression enhanced the inhibitory effect of Slit2 on tumor metastasis (XREF_FIG, XREF_SUPPLEMENTARY).
USP33 increases the amount of SLIT2.
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USP33 increases the amount of SLIT2. 1 / 1
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USP33 silencing in A549 and SPC-A-1 cells significantly promoted the cell migration, invasion and metastasis and obviously down-regulated the expressions of SLIT2 and ROBO1.
USP33 activates SLIT2.
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USP33 activates SLIT2. 1 / 1
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Moreover, studies have shown that USP33 mediated SLIT2 and ROBO1 signalling participates in the development of cancer [XREF_BIBR, XREF_BIBR].
USP33 affects ARRB2
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USP33 decreases the amount of ARRB2.
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USP33 decreases the amount of ARRB2. 2 / 2
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Further experiments revealed that USP33 silencing, which increased the ubiquitination level of beta-arrestin2, can lead to non degradative effects towards this scaffold protein, but augment the endocytosis of ligand binding CXCR4.

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The IHC results also indicated that USP33 may not directly regulate the expression or degradation of beta-arrestin2.
USP33 increases the amount of ARRB2.
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USP33 increases the amount of ARRB2. 1 / 1
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Moreover, USP33 knock-down can significantly increase the ubiquitination level of beta-arrestin2 under SDF-1 stimulation.
HERC2 affects USP33
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HERC2 inhibits USP33.
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HERC2 inhibits USP33. 1 / 1
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HERC2 knockdown increased levels of the USP33 protein and decreased levels of the p21 protein.
HERC2 increases the amount of USP33.
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HERC2 increases the amount of USP33. 1 / 1
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Knockdown of HERC2 increased the levels of USP33, confirming that HERC2 functions as an ubiquitin ligase for USP33.
HERC2 activates USP33.
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HERC2 activates USP33. 1 / 1
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In favour of the hypothesis that HectPH1 might regulate cAR1 signaling, rather recently it has been reported in mammalian cells that HERC2 targets the deubiquitinating enzyme USP33, which is involved in regulating beta2 adrenergic receptor recycling and re-sensitization [XREF_BIBR].
Vinclozolin affects USP33
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Vinclozolin increases the amount of USP33. 2 / 2
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No evidence text available

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Dihydroartemisinin decreases the amount of USP33. 2 / 2
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In this study, it was shown that DHA reduced the expression level of RalB and USP33 in three different types of cancer cells.

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Mechanistically, we found that DHA degraded RalB, inhibited USP33 expression, and triggered autophagy.
USP33 affects cell growth
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MTT results showed that USP33 can inhibit cellular growth (XREF_FIG).

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Unlike USP33, which has been reported to inhibit mitogen activated protein kinase (MAPK) activation pathway and suppress hepatoma cell growth 26, our study suggests that USP21 activates ERK1/2 to promote HCC cell proliferation.
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More importantly, DUSP1 overexpression could reverse the USP33 knockdown induced JNK activation and apoptosis in docetaxel treated prostate cancer cells.

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Ubiquitin specific peptidase 33 promotes cell proliferation and reduces apoptosis through regulation of the SP1/PI3K/AKT pathway in retinoblastoma.
USP33 affects MET
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USP33 activates MET. 2 / 2
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Mechanistically , USP33 directly bound SP1 and decreased its ubiquitination , thereby upregulating c-Met expression .

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We found that USP33 knockdown inhibited the invasion and metastasis in HCC cells both in vitro and in vivo , which was partly dependent on c-Met .
USP33 affects DUSP1
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USP33 activates DUSP1. 2 / 2
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Therefore, USP33 overexpression in prostate cancer may contribute to docetaxel resistance by inhibiting the degradation of its partner DUSP1, leading to impaired JNK activation and apoptosis.

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Furthermore, we found that USP33 could interact with the phosphatase DUSP1 to negatively regulate the activation of JNK, while USP33 knockdown promoted the proteasomal degradation of DUSP1.
Copper atom affects USP33
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Copper atom increases the amount of USP33.
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Copper atom increases the amount of USP33. 1 / 1
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ctd
No evidence text available
Copper atom decreases the amount of USP33.
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Copper atom decreases the amount of USP33. 1 / 1
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USP33 affects USP33
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USP33 bound to BTRC inhibits USP33. 1 / 1
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We also revealed that beta-TrCP interacted with USP33 independently of the classic binding motif for beta-TrCP, and mediated USP33 degradation via the ubiquitin proteasome pathway.
USP33 inhibits USP33. 1 / 1
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Furthermore, beta-TrCP also increased the ubiquitination of USP33 (^ DSG) and decreased the protein stability of USP33 (^ DSG).
USP33 affects JNK
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USP33 bound to DUSP1 inhibits JNK. 1 / 1
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Furthermore, we found that USP33 could interact with the phosphatase DUSP1 to negatively regulate the activation of JNK, while USP33 knockdown promoted the proteasomal degradation of DUSP1.
USP33 inhibits JNK. 1 / 1
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More importantly, DUSP1 overexpression could reverse the USP33 knockdown induced JNK activation and apoptosis in docetaxel treated prostate cancer cells.
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E3_Ub_ligase increases the amount of USP33.
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E3_Ub_ligase increases the amount of USP33. 1 / 1
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However, how cellular USP33 levels are regulated remains largely unexplored.Here we discovered that the E3 ligase beta-TrCP did not reduce USP33 mRNA levels, but significantly downregulated USP33 prot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
E3_Ub_ligase decreases the amount of USP33.
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E3_Ub_ligase decreases the amount of USP33. 1 / 1
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However, how cellular USP33 levels are regulated remains largely unexplored.Here we discovered that the E3 ligase beta-TrCP did not reduce USP33 mRNA levels, but significantly downregulated USP33 prot[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
Vasopressin affects USP33
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However, vasopressin (V 2 R agonist) promoted dissociation of beta-arrestin2 and USP33.
Valdecoxib affects USP33
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Valdecoxib increases the amount of USP33. 1 / 1
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Trichloroethene decreases the amount of USP33. 1 / 1
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Thapsigargin increases the amount of USP33. 1 / 1
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Tetrachloromethane increases the amount of USP33. 1 / 1
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Sulforaphane decreases the amount of USP33. 1 / 1
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Selenium atom decreases the amount of USP33. 1 / 1
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Schizandrin B increases the amount of USP33. 1 / 1
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Phlorizin affects USP33
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Phlorizin decreases the amount of USP33. 1 / 1
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Mono(2-ethylhexyl) phthalate decreases the amount of USP33. 1 / 1
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Mitochondrial DNA damage affects USP33
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Mitochondrial DNA damage decreases the amount of USP33. 1 / 1
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bel
To better understand the consequences of mtDNA deletions, we microarrayed six cell types containing mtDNA deletions from KSS and CPEO patients. Indicated are transcripts shared and downregulated in cells harboring mtDNA deletions in >3 experiments (Table 4); Differentially expressed genes were identified by comparing GeneChips designated as baseline (muscles, myoblasts, fibroblasts, and lymphoblasts from healthy subjects, fusion control cell lines, and parental 143B cells) with the ones that represent the experimental parameters (muscles, myoblasts, fibroblasts, and lymphoblasts from patients, mutant cybrids, and 143B rho zero cells) using a difference in mean fluorescence ? 30 and a P value < 0.05; 37 downregulated genes; 26 upregulated genes;
Methyl methanesulfonate increases the amount of USP33. 1 / 1
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Methamphetamine decreases the amount of USP33. 1 / 1
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Jinfukang affects USP33
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Jinfukang decreases the amount of USP33. 1 / 1
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Indometacin affects USP33
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Indometacin increases the amount of USP33. 1 / 1
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Hydroxyurea affects USP33
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Further, we investigated whether USP33 depletion could affect centrosome reduplication in cells treated with hydroxyurea to induce prolonged S-phase.
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Hydroperoxide decreases the amount of USP33. 1 / 1
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Hydralazine affects USP33
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Hydralazine increases the amount of USP33. 1 / 1
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Hsa-miR-877-5p decreases the amount of USP33. 1 / 1
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Hsa-miR-148b-3p decreases the amount of USP33. 1 / 1
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biopax:mirtarbase
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Hsa-miR-1-3p decreases the amount of USP33. 1 / 1
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biopax:mirtarbase
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Gold atom affects USP33
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Gold atom decreases the amount of USP33. 1 / 1
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Gentamycin affects USP33
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Gentamycin increases the amount of USP33. 1 / 1
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Flutamide affects USP33
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Flutamide increases the amount of USP33. 1 / 1
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Fbxw1 affects USP33
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Fbxw1 decreases the amount of USP33. 1 / 1
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We noticed that endogenous USP33 protein levels were gradually downregulated by HA-beta-TrCP in a dose dependent manner.
Dicrotophos affects USP33
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Dicrotophos decreases the amount of USP33. 1 / 1
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Diazinon affects USP33
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Diazinon increases the amount of USP33. 1 / 1
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Dexamethasone increases the amount of USP33. 1 / 1
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Cyclosporin A decreases the amount of USP33. 1 / 1
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Copper(II) sulfate decreases the amount of USP33. 1 / 1
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Cobalt dichloride increases the amount of USP33. 1 / 1
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Chlorpyrifos decreases the amount of USP33. 1 / 1
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Bisphenol F affects USP33
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Bisphenol F increases the amount of USP33. 1 / 1
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Bisphenol A affects USP33
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Bisphenol A increases the amount of USP33. 1 / 1
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Autophagy affects USP33
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These results suggested that enhanced autophagy can inhibit the expression of USP33 .
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Aflatoxin M1 decreases the amount of USP33. 1 / 1
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Vitamin E affects USP33
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Vitamin E decreases the amount of USP33. 1 / 1
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VHL affects USP33
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VHL activates USP33. 1 / 1
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Targeted degradation of VDU1 by pVHL could be crucial for regulating the ubiquitin-proteasome degradation pathway.
Ubiquitin affects USP33
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The inhibitory function of Slit2-Robo1 is mediated by ubiquitin specific protease 33 (USP33) via deubiquitinating and stabilizing Robo1.

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It has been reported that USP33 can promote the internalization of beta2-adrenergic receptor and vasopressin receptor 2 [XREF_BIBR, XREF_BIBR].
USP33 affects proteolysis
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Finally, CDK2 inhibitor response was enhanced when combined with knockdown of the deubiquitinase USP33 that in turn accelerates CP110 protein degradation.

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VDU1 and VDU2, a closely related isoform, have been shown to increase half-life of type 2 iodothyronine deiodinase by their deubiquitinating activity [23].
USP33 affects hydroxyurea
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Similar to CP110 ablation 2, depletion of USP33 significantly inhibited hydroxyurea (HU)-induced centrosome amplification in two cell lines (XREF_FIG and XREF_SUPPLEMENTARY).

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More importantly, DUSP1 overexpression could reverse the USP33 knockdown induced JNK activation and apoptosis in docetaxel treated prostate cancer cells.

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Similarly, USP33 promotes centrosome biogenesis via specific and potent stabilization of the centriolar coiled coil protein CP110, and USP22 has been found to strengthen the NAD dependent histone deacetylase Sirt1 to antagonize p53 activation.
USP33 affects autophagy
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Mechanistically, we found that DHA degraded RalB, inhibited USP33 expression, and triggered autophagy.
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Mechanistically , USP33 directly bound SP1 and decreased its ubiquitination , thereby upregulating c-Met expression .
USP33 affects TWIST1
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Modified USP33 decreases the amount of TWIST1. 1 / 1
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We found that USP33 overexpression can significantly down-regulate the protein level of beta-catenin, snai1, slug, twist1, and N-cadherin, while increasing the E-cadherin expression.
USP33 affects RB1
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USP33 activates RB1. 1 / 1
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This study uncovered that USP33 promoted the progression of RB through regulation of the SP1/PI3K/AKT pathway.
USP33 affects MYC
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USP33 increases the amount of MYC. 1 / 1
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USP33 knockdown significantly reduced c-Myc protein expression (XREF_FIG), but did not affect c-Myc mRNA expression (XREF_FIG).
USP33 affects MAPK
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USP33 inhibits MAPK. 1 / 1
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Unlike USP33, which has been reported to inhibit mitogen activated protein kinase (MAPK) activation pathway and suppress hepatoma cell growth 26, our study suggests that USP21 activates ERK1/2 to promote HCC cell proliferation.
USP33 affects KITLG
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USP33 inhibits KITLG. 1 / 1
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CP110 is also regulated by the deubiquitinase USP33, which antagonizes SCF CyclinF activity during S and G2/M to stabilize CP110, causing mitotic abnormalities [XREF_BIBR].
USP33 affects IRF9
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USP33 increases the amount of IRF9. 1 / 1
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microRNAs gets internalized by human microglia and suppress target gene expression of USP33 (Ubiquitin Specific peptidase 33) and downstream IRF9 levels.
USP33 affects HDAC2
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USP33 activates HDAC2. 1 / 1
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Whilst USP33 or USPL1 depletion increased the HDAC2 and HDAC1 ratio, we identified USP27X and the tumor suppressor BAP1 as DUBs whose depletion lead to the most significant decrease in the HDAC2 and HDAC1 ratio.
USP33 affects HDAC1
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USP33 activates HDAC1. 1 / 1
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Whilst USP33 or USPL1 depletion increased the HDAC2 and HDAC1 ratio, we identified USP27X and the tumor suppressor BAP1 as DUBs whose depletion lead to the most significant decrease in the HDAC2 and HDAC1 ratio.
USP33 affects ERK
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USP33 activates ERK. 1 / 1
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Interestingly, our results demonstrated that USP33 knock-down can significantly increase the " late " ERK activation induced by SDF- 1.
USP33 affects Cyclin
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USP33 inhibits Cyclin. 1 / 1
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In this study, USP33 knockdown was achieved as a proof-of-concept because USP33 can antagonize cyclin F actions on CP110 in regulating centrosome duplication, maturation and separation.
USP33 affects CDH2
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Modified USP33 decreases the amount of CDH2. 1 / 1
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We found that USP33 overexpression can significantly down-regulate the protein level of beta-catenin, snai1, slug, twist1, and N-cadherin, while increasing the E-cadherin expression.
USP33 affects AVPR2
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USP33 inhibits AVPR2. 1 / 1
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While USP33 overexpression blocked the cointernalization of beta-arrestin with activated V 2 R on endosomes and curtailed ERK activation mediated by beta-arrestin, knockdown of endogenously expressed [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
USP33 affects ATF3
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USP33 activates ATF3. 1 / 1
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Reduced USP33 in turn decreases the stability of cellular ATF3 protein via deubiquitylation.
USP33 affects ADRB2
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USP33 activates ADRB2. 1 / 1
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It has been reported that USP33 can promote the internalization of beta2-adrenergic receptor and vasopressin receptor 2 [XREF_BIBR, XREF_BIBR].
USP20 affects USP33
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USP20 activates USP33. 1 / 1
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The closely related DUBs, USP20 and USP33, deubiquitylate activated beta-adrenergic receptors as well as the adaptor and signalling protein beta-arrestin (in the case of USP33), to favour recycling from endosomes, despite largely being associated with the secretory pathway 75, 76, 77.
SP1 affects USP33
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SP1 inhibits USP33. 1 / 1
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SP1 overexpression abolished the roles of USP33 downregulation in modulating the activation of PI3K/AKT signaling, cell growth, apoptosis, and cell cycle.
RALB affects USP33
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RALB activates USP33. 1 / 1
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Mechanistically , we found that DHA degraded RalB , inhibited USP33 expression , and triggered autophagy .
Protease affects USP33
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The inhibitory function of Slit2-Robo1 is mediated by ubiquitin specific protease 33 (USP33) via deubiquitinating and stabilizing Robo1.
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Plant Extracts increases the amount of USP33. 1 / 1
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Norepinephrine affects USP33
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Norepinephrine increases the amount of USP33. 1 / 1
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VDU1, but not VDU2, is markedly increased in brown adipocytes by norepinephrine or cold exposure, further amplifying the increase in D2 activity that results from catecholamine-stimulated de novo synthesis.

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Our results showed that MG132 blocked beta-TrCP-mediated USP33 downregulation, suggesting that beta-TrCP promotes USP33 downregulation via the proteasome pathway.
MIR148A affects USP33
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MiR-590 can directly target IRF9 while miR-148a suppresses USP33 expression levels in human microglia .
| PMC
JNK affects USP33
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JNK activates USP33. 1 / 1
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More importantly, DUSP1 overexpression could reverse the USP33 knockdown-induced JNK activation and apoptosis in docetaxel-treated prostate cancer cells.
IL6 affects USP33
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IL6 increases the amount of USP33. 1 / 1
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IL-6 stimulation of the cells obviously enhanced the expression of USP33.
DIO2 affects USP33
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DIO2 deubiquitinates USP33. 1 / 1
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DIO2 works as a dimer that associates with Hedgehog inducible ubiquitin ligase WD repeat and SOCS box containing 1 (WSB-1) [XREF_BIBR], ubiquitin conjugases UBC6 and UBC-7 [XREF_BIBR], and DIO2 specific deubiquitinating enzymes ubiquitin specific peptidase 20 (USP20), and ubiquitin specific peptidase 33 (USP33) [XREF_BIBR].
CCP110 affects USP33
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CCP110 inhibits USP33. 1 / 1
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We found that centrosomal targeting of USP33 is partially dependent on CP110 because depletion of CP110 reduced USP33 localization to centrosomes (see below) (XREF_SUPPLEMENTARY).
BAAT affects USP33
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