USP43 Data Analysis

HGNC Gene Name
ubiquitin specific peptidase 43
HGNC Gene Symbol
USP43
Identifiers
hgnc:20072 NCBIGene:124739 uniprot:Q70EL4
Orthologs
mgi:2444541 rgd:2303824
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for USP43
Number of Papers
8 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

Dependency GO Term Enrichment

Gene set enrichment analysis was done on the genes correlated with USP43using 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 USP43 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
USP43 deubiquitinates ZEB1. 2 / 2
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Meanwhile, USP43 can deubiquitinate and stabilize the ZEB1 protein, which plays an important role in the function of colorectal cancer.

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USP43 could promote cell proliferation, invasion, and migration in colorectal cancer by regulating ZEB1 ubiquitylation degradation.

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

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USP43 could promote the proliferation, migration, and invasion of colorectal cancer.

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USP43 knockdown in SW480 cells could significantly reduce cell proliferation.

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USP43 promotes proliferation of colorectal cancer cells in vitro.

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For cell proliferation analysis, USP43 knockdown in SW480 cells could significantly reduce cell proliferation compared with those in normal SW480 cells on days 2, 3, 4, 5 (P < 0.01).

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USP43 could promote cell proliferation , invasion , and migration in colorectal cancer by regulating ZEB1 ubiquitylation degradation .

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Meanwhile, Figure XREF_FIG C and XREF_FIG D suggested that knockdown and over-expression treatment of ZEB1 gene treatments could effectively inhibit and promote cell proliferation caused by USP43 overexpression and knockdown treatments, respectively.

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Meanwhile, USP43 overexpression in DLD1 cells could significantly promote cell proliferation in vitro.

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However, USP43 overexpression in DLD1 cells could significantly promote cell proliferation compared with those in vector treated DLD1 cells on days 2, 3, 4, 5 (P < 0.05).
USP43 affects ZEB1
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USP43 activates ZEB1.
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USP43 activates ZEB1. 5 / 5
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Meanwhile, USP43 knockdown treated SW480 cells could significantly decrease the remaining ZEB1 protein in cells compared to that normal SW480 cells (P < 0.01).

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USP43 directly regulates ZEB1 protein, mediating proliferation and metastasis of colorectal cancer.

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Meanwhile, USP43 overexpression treated DLD1 cells could significantly decrease the degradation of the remaining ZEB1 protein in cells compared to that normal DLD1 cells (P < 0.01).

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The results suggested that USP43 knockdown treated SW480 cells could significantly promote the degradation of the remaining ZEB1 protein in cells compared to that normal SW480 cells (P < 0.01).

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Figure XREF_FIG K and 5L suggested that USP43 overexpression in DLD1 cells could significantly promote the remaining ZEB1 protein in cells compared to that normal DLD1 cells (P < 0.01).
USP43 decreases the amount of ZEB1.
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USP43 decreases the amount of ZEB1. 1 / 1
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Moreover, USP43 can reduce ZEB1 protein expression without affecting its transcription.

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USP43 could promote the proliferation, migration, and invasion of colorectal cancer.

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USP43 knockdown in SW480 cells could significantly inhibit cell migration and invasion compared to that in the normal SW480 cells (P < 0.01).

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USP43 could promote cell proliferation , invasion , and migration in colorectal cancer by regulating ZEB1 ubiquitylation degradation .

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Meanwhile, ZEB1overexpression could effectively reverse the changes in invasion caused by USP43 overexpression in SW480 cells (P < 0.01).

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However, USP43 overexpression in DLD1 cells could promote cell migration and invasion compared to that in the normal DLD1 cells (P < 0.01).
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Valproic acid increases the amount of USP43. 4 / 4
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USP43 affects VIM
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USP43 increases the amount of VIM. 2 / 2
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USP43 knockdown in SW480 cells could effectively inhibit protein expressions of N-cadherin and Vimentin (P < 0.01).

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Meanwhile, USP43 knockdown in SW480 cells could inhibit and promote the protein expressions of N-cadherin and Vimentin and protein expressions of N-cadherin, respectively.
Modified USP43 increases the amount of VIM. 2 / 2
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Moreover, USP43 overexpression in DLD1 cells could effectively increase protein expressions of N-cadherin and Vimentin (P < 0.01).

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Therefore, USP43 overexpression in DLD1 cells could promote and inhibit the protein expressions of N-cadherin and Vimentin and protein expressions of N-cadherin, respectively.
USP43 affects CDH2
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Modified USP43 increases the amount of CDH2. 2 / 2
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Moreover, USP43 overexpression in DLD1 cells could effectively increase protein expressions of N-cadherin and Vimentin (P < 0.01).

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Therefore, USP43 overexpression in DLD1 cells could promote and inhibit the protein expressions of N-cadherin and Vimentin and protein expressions of N-cadherin, respectively.
USP43 increases the amount of CDH2. 2 / 2
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Meanwhile, USP43 knockdown in SW480 cells could inhibit and promote the protein expressions of N-cadherin and Vimentin and protein expressions of N-cadherin, respectively.

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USP43 knockdown in SW480 cells could effectively inhibit protein expressions of N-cadherin and Vimentin (P < 0.01).
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USP43 activates Cell Survival.
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The results suggested that USP43 knockdown treated SW480 cells could significantly decrease cell survival in three different drug treatments compared with that in normal SW480 cells (P < 0.05).

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However, USP43 overexpression in DLD1 cells could effectively promote cell survival in three different drug treatments compared with that in normal DLD1 cells (P < 0.05).
USP43 inhibits Cell Survival.
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Figure XREF_FIG G and Figure XREF_FIG H suggested that ZEB1 over-expression and knockdown treatments could effectively reverse the changes in cell survival rate caused by USP43 knockdown and overexpression treatment in the chemotherapy sensitivity analysis (P < 0.01).
Vorinostat affects USP43
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Vorinostat increases the amount of USP43. 2 / 2
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Phenylmercury acetate increases the amount of USP43. 2 / 2
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P-chloromercuribenzoic acid increases the amount of USP43. 2 / 2
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Entinostat affects USP43
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Entinostat increases the amount of USP43. 2 / 2
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Bisphenol A affects USP43
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Bisphenol A decreases the amount of USP43. 2 / 2
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USP43 knockdown in SW480 cells could significantly inhibit cell migration and invasion compared to that in the normal SW480 cells (P < 0.01).

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However, USP43 overexpression in DLD1 cells could promote cell migration and invasion compared to that in the normal DLD1 cells (P < 0.01).

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We show that USP43 strongly suppresses the growth and metastasis of breast cancer in vivo.

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Meanwhile, previous study indicated that USP43 could remarkably inhibit the growth and metastasis of breast cancer though affecting EGFR/PI3K/AKT XREF_BIBR.
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Pirinixic acid decreases the amount of USP43.
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Pirinixic acid decreases the amount of USP43. 1 / 1
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Pirinixic acid activates USP43.
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Aflatoxin B1 increases the amount of USP43.
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Aflatoxin B1 increases the amount of USP43. 1 / 1
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Aflatoxin B1 decreases the amount of USP43.
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Aflatoxin B1 decreases the amount of USP43. 1 / 1
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USP43 affects CDH1
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Modified USP43 decreases the amount of CDH1. 1 / 1
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However, USP43 overexpression in DLD1 cells could effectively inhibit E-cadherin protein expressions (P < 0.01).
USP43 decreases the amount of CDH1. 1 / 1
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However, USP43 knockdown in SW480 cells could effectively promote protein expressions of E-cadherin (P < 0.01).
6-propyl-2-thiouracil increases the amount of USP43.
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6-propyl-2-thiouracil increases the amount of USP43. 1 / 1
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6-propyl-2-thiouracil decreases the amount of USP43.
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6-propyl-2-thiouracil decreases the amount of USP43. 1 / 1
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Titanium dioxide increases the amount of USP43. 1 / 1
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Thioacetamide increases the amount of USP43. 1 / 1
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Tetrachloromethane increases the amount of USP43. 1 / 1
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Sulforaphane decreases the amount of USP43. 1 / 1
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Sodium dodecyl sulfate increases the amount of USP43. 1 / 1
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Rosiglitazone increases the amount of USP43. 1 / 1
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Quinolin-8-ol decreases the amount of USP43. 1 / 1
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Quercetin affects USP43
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Quercetin decreases the amount of USP43. 1 / 1
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Paracetamol affects USP43
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Paracetamol decreases the amount of USP43. 1 / 1
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Panobinostat increases the amount of USP43. 1 / 1
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Nickel monoxide increases the amount of USP43. 1 / 1
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Mercury dibromide increases the amount of USP43. 1 / 1
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Manganese(II) chloride increases the amount of USP43. 1 / 1
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Leflunomide affects USP43
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Leflunomide increases the amount of USP43. 1 / 1
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Ketamine affects USP43
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Ketamine decreases the amount of USP43. 1 / 1
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Jinfukang affects USP43
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Jinfukang decreases the amount of USP43. 1 / 1
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Dorsomorphin increases the amount of USP43. 1 / 1
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Decabromodiphenyl ether increases the amount of USP43. 1 / 1
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Clothianidin decreases the amount of USP43. 1 / 1
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Cisplatin affects USP43
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Cisplatin decreases the amount of USP43. 1 / 1
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Chloroprene affects USP43
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Chloroprene increases the amount of USP43. 1 / 1
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Bis(2-ethylhexyl) phthalate increases the amount of USP43. 1 / 1
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Acetamide affects USP43
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Acetamide increases the amount of USP43. 1 / 1
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Abrine affects USP43
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Abrine increases the amount of USP43. 1 / 1
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In addition, USP43 could promote tumorigenesis by regulating cell cycle and EMT process in breast cancer XREF_BIBR.
USP43 affects cell cycle
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In addition, USP43 could promote tumorigenesis by regulating cell cycle and EMT process in breast cancer XREF_BIBR.
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Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619.
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In addition , USP43 could promote tumorigenesis by regulating cell cycle and EMT process in breast cancer 14 .
PCB 180 affects USP43
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PCB 180 increases the amount of USP43. 1 / 1
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Dietary Fats increases the amount of USP43. 1 / 1
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2,4,4'-trichlorobiphenyl increases the amount of USP43. 1 / 1
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