MINDY3 Data Analysis

HGNC Gene Name
MINDY lysine 48 deubiquitinase 3
HGNC Gene Symbol
MINDY3
Identifiers
hgnc:23578 NCBIGene:80013 uniprot:Q9H8M7
Orthologs
mgi:1914210 rgd:1309605
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for MINDY3
Number of Papers
2 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 MINDY3using 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 MINDY3 from literature and knowledge bases. The first section shows only DUB activity and the second shows all other results.

Deubiquitinase Activity

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
| 10
| 9

reach
In the present study, our data showed that elevated CARP expression led to significantly increased apoptosis and decreased proliferation in BGC-823 cells, which suggested that CARP partly inhibits tumor progression via precise regulation of the balance of the cell growth and death.

reach
To determine whether over-expression of CARP alone can induce cell apoptosis, A549 cells and HEK293S cells were stably transfected with control plasmid or plasmids carrying CARP or antisense-CARP, res[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
Similar results were observed by MTT assay.Since over-expression of CARP induces weak apoptosis, we tested if over-expression of CARP can inhibit tumor cell line growth.

reach
Full length CARP cDNA induced weakly apoptosis in the absence of additional apoptotic signals (Figs. 5B and 6C); however, the deleted-CARP had no apoptotic activity, suggesting that intact CARD domain[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
To determine if CARP induced apoptosis and inhibition of cell growth requires intact CARD, HEK293S cells, ECV304 cells, and A549 cells were stably transfected with CARP, CARP-MYC, deleted-CARP, antise[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]

reach
We therefore examined whether cellular CARP is able to induce apoptosis when over-expressed in human cells.

reach
Studies on the biological function of CARP have proved that overexpression of CARP could significantly promote apoptosis in lung carcinoma A549 and human embryonic kidney HEK293s cells, and inhibit cell proliferation in lung carcinoma A549 and PG, melanoma WM451, prostate cancer PC-3 and PC-3M, liver cancer H7402, and bladder cancer BIU87 cells XREF_BIBR, suggesting that CARP is a pro apoptotic protein and has potential anti-tumor effects.

reach
The ectopic expression of CARP in H9c2 cells increased the resistance to hypoxia induced apoptosis.

reach
XREF_FIG shows stable transfection of CARP induced cell apoptosis.
| 1

reach
CARP gene silencing inhibits tumor cell survival and increases cancer cell sensitivity to the death ligand or chemotherapy induced apoptosis.

reach
We found that overexpression of CARP significantly inhibited proliferation of BGC-823 cells (XREF_FIG).

reach
The cell proliferation was significantly inhibited by 1.2-5 folds (P < 0.02) in seven CARP transfected tumor cell lines-lung carcinoma A549 and PG, melanoma WM451, prostate cancer PC-3 and PC-3M, liver cancer H7402, and bladder cancer BIU87.

reach
Studies on the biological function of CARP have proved that overexpression of CARP could significantly promote apoptosis in lung carcinoma A549 and human embryonic kidney HEK293s cells, and inhibit cell proliferation in lung carcinoma A549 and PG, melanoma WM451, prostate cancer PC-3 and PC-3M, liver cancer H7402, and bladder cancer BIU87 cells XREF_BIBR, suggesting that CARP is a pro apoptotic protein and has potential anti-tumor effects.

reach
We found that over-expression of CARP significantly inhibits proliferation of tumor cell lines examined except two breast cancer cell lines.

reach
Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage independent growth in soft agar) and motility (migration and adhesion).

reach
In the present study, our data showed that elevated CARP expression led to significantly increased apoptosis and decreased proliferation in BGC-823 cells, which suggested that CARP partly inhibits tumor progression via precise regulation of the balance of the cell growth and death.

reach
As shown in Fig. 6, the cell counting results showed that over-expression of CARP or CARP-MYC significantly inhibits proliferation while antisense-CARP, blocking CARP mRNA expression, stimulates proli[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MINDY3 affects CDKN1B
| 1 5
MINDY3 activates CDKN1B.
| 1 2
MINDY3 activates CDKN1B. 3 / 3
| 1 2

reach
In summary (XREF_FIG), we have shown that (a) CARP is downregulated in stomach cancer tissues; (b) CARP functioned as a tumor suppressor by inducing apoptosis, and inhibiting proliferation, migration and adhesion; (c) CARP might cause G1 arrest by promoting p27 and p21 nuclei location, and inhibits cyclin-E and CDK2 activities; (d) rs2297882 in the CARP Kozak sequence is associated with the downregulation of CARP expression and with the susceptibility to stomach cancer.

sparser
A similar tendency in the changes of these proteins expression levels were observed in A549 cells, suggesting that CARP-induced p27 activation was responsible for CARP-induced G1 arrest and blockage of the G1/S transition.

reach
A similar tendency in the changes of these proteins expression levels were observed in A549 cells, suggesting that CARP induced p27 activation was responsible for CARP induced G1 arrest and blockage of the G1/S transition.
MINDY3 increases the amount of CDKN1B.
| 2
MINDY3 increases the amount of CDKN1B. 1 / 1
| 1

reach
Our study results indicated that overexpression of CARP induced an increase in p27 accompanied with decreases in cyclin-E and CDK2, and the siRNA directed CARP gene silence inhibited p27 expression and unregulated the expression of cyclin-E and CDK2.
Modified MINDY3 increases the amount of CDKN1B. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
MINDY3 decreases the amount of CDKN1B.
| 1
Modified MINDY3 decreases the amount of CDKN1B. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
5 |
Valproic acid increases the amount of MINDY3. 5 / 5
5 |

ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available

ctd
No evidence text available
| 2 2
| 2 2

sparser
Next, we also demonstrated that overexpressed CARP dramatically inhibited the adhesion of BGC-823 cells to artificial basement membranes.

reach
The results of cell-matrix adhesion assay showed that CARP inhibited the adhesion to matrigel of BGC-823 cells, and the adhesion ability was decreased more than 50% (XREF_FIG).

reach
Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage independent growth in soft agar) and motility (migration and adhesion).

sparser
The results of cell-matrix adhesion assay showed that CARP inhibited the adhesion to matrigel of BGC-823 cells, and the adhesion ability was decreased more than 50% ( xref ).
MINDY3 affects TP53
| 4
MINDY3 decreases the amount of TP53.
| 2
Modified MINDY3 decreases the amount of TP53. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
MINDY3 decreases the amount of TP53. 1 / 1
| 1

reach
CARP silencing stimulates p53 expression and promotes downstream effects, including transcriptional activation and tumor suppression.
MINDY3 increases the amount of TP53.
| 1
Modified MINDY3 increases the amount of TP53. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
MINDY3 activates TP53.
| 1
MINDY3 activates TP53. 1 / 1
| 1

reach
The results of western blot analysis showed CARP induced upregulation of p53, suggesting that the accumulation of its direct targets in the nuclei, such as Bax, may contribute to the increase in apoptosis.
MINDY3 affects CDKN1A
| 3
MINDY3 increases the amount of CDKN1A.
| 1
Modified MINDY3 increases the amount of CDKN1A. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
MINDY3 decreases the amount of CDKN1A.
| 1
Modified MINDY3 decreases the amount of CDKN1A. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
MINDY3 activates CDKN1A.
| 1
MINDY3 activates CDKN1A. 1 / 1
| 1

reach
In summary (XREF_FIG), we have shown that (a) CARP is downregulated in stomach cancer tissues; (b) CARP functioned as a tumor suppressor by inducing apoptosis, and inhibiting proliferation, migration and adhesion; (c) CARP might cause G1 arrest by promoting p27 and p21 nuclei location, and inhibits cyclin-E and CDK2 activities; (d) rs2297882 in the CARP Kozak sequence is associated with the downregulation of CARP expression and with the susceptibility to stomach cancer.
MINDY3 affects CDK2
| 3
MINDY3 inhibits CDK2.
| 1
MINDY3 inhibits CDK2. 1 / 1
| 1

reach
In summary (XREF_FIG), we have shown that (a) CARP is downregulated in stomach cancer tissues; (b) CARP functioned as a tumor suppressor by inducing apoptosis, and inhibiting proliferation, migration and adhesion; (c) CARP might cause G1 arrest by promoting p27 and p21 nuclei location, and inhibits cyclin-E and CDK2 activities; (d) rs2297882 in the CARP Kozak sequence is associated with the downregulation of CARP expression and with the susceptibility to stomach cancer.
MINDY3 increases the amount of CDK2.
| 1
MINDY3 increases the amount of CDK2. 1 / 1
| 1

reach
Our study results indicated that overexpression of CARP induced an increase in p27 accompanied with decreases in cyclin-E and CDK2, and the siRNA directed CARP gene silence inhibited p27 expression and unregulated the expression of cyclin-E and CDK2.
MINDY3 decreases the amount of CDK2.
| 1
Modified MINDY3 decreases the amount of CDK2. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
2 |
Indometacin increases the amount of MINDY3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
2 |
Cyclosporin A increases the amount of MINDY3. 2 / 2
2 |

ctd
No evidence text available

ctd
No evidence text available
| 2
| 2

reach
Aloe-emodin induces destabilization of caspase-8 and -10-associated RING protein (CARP) mRNA, indicating that caspase-8–mediated p53-independent apoptosis in human carcinoma cells [75] and human nasopharyngeal carcinoma cells induces caspase-3, -8, and -9–mediated activation of the mitochondrial death pathway [76].

reach
Aloe-emodin induces destabilization of caspase-8 and -10-associated RING protein (CARP) mRNA, indicating that caspase-8emediated p53-independent apoptosis in human carcinoma cells [75] and human nasopharyngeal carcinoma cells induces caspase-3, -8, and -9emediated activation of the mitochondrial death pathway [76] .
2 |

ctd
No evidence text available

ctd
No evidence text available
Methyl methanesulfonate increases the amount of MINDY3.
1 |
Methyl methanesulfonate increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Methyl methanesulfonate decreases the amount of MINDY3.
1 |
Methyl methanesulfonate decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
| 1
| 1

reach
WA treatments also stimulated expression of the cell cycle and apoptosis regulatory protein (CARP)-1/CCAR1, a novel transducer of cell growth signaling.
1 |
Troglitazone increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available

ctd
No evidence text available
Sunitinib affects MINDY3
1 |
Sunitinib increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Sodium arsenite increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Progesterone increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |

ctd
No evidence text available
Nefazodone affects MINDY3
1 |
Nefazodone decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Ionomycin affects MINDY3
1 |
Ionomycin decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Hsa-miR-183-5p decreases the amount of MINDY3. 1 / 1
1 |

biopax:mirtarbase
No evidence text available
Gentamycin affects MINDY3
1 |
Gentamycin increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Formaldehyde increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Flutamide affects MINDY3
1 |
Flutamide decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Ethyl methanesulfonate increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Dorsomorphin increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Dibutyl phthalate increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Dexamethasone increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Cisplatin affects MINDY3
1 |
Cisplatin increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Chlorpyrifos increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Carbon nanotube increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1 |
Bisphenol A increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Atrazine affects MINDY3
1 |
Atrazine decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
Soman affects MINDY3
1 |
Soman decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
PFU affects MINDY3
| 1
PFU activates MINDY3. 1 / 1
| 1

reach
Mahoney Virus in PFU CHAT Virus in PFU produced at 40 1 113 113 113 113 113 113 113 02 203 203 203 203 203 203 0 3 X 102 3 X 103 104 3 X 104 105 3 X 105 3 X 1050 2 X 108 6 X 103 2 X 104 6 X 104 2 X 10[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
N-nitrosodimethylamine increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
| 1
| 1

reach
Overexpression of C10ORF97 significantly suppressed human lung carcinoma A549 cell growth (proliferation and anchorage independent growth in soft agar) and motility (migration and adhesion).
MINDY3 affects cell cycle
| 1
| 1

reach
CARP modulated the cell cycle and the expression of several cell-cycle regulators.
MINDY3 affects bortezomib
| 1
| 1

reach
Since, CCAR1 and CARP -1 is an emerging and novel target of diverse cell growth and apoptosis signaling pathways [XREF_BIBR, XREF_BIBR - XREF_BIBR] and is not involved in cisplatin dependent HBC growth inhibition [XREF_BIBR], our identification of novel Velcade targets such as CCAR1 and CARP -1 has potential to allow for design of effective anti-MPM strategies for optimizing Velcade utility in a range of MPM including the drug (Cisplatin)-resistant phenotype.

reach
Taken together, these findings strongly support that CARP suppresses tumor progression by decreasing the invasion and metastatic abilities of tumor cells.
| 1

reach
Studies on the biological function of CARP have proved that overexpression of CARP could significantly promote apoptosis in lung carcinoma A549 and human embryonic kidney HEK293s cells, and inhibit cell proliferation in lung carcinoma A549 and PG, melanoma WM451, prostate cancer PC-3 and PC-3M, liver cancer H7402, and bladder cancer BIU87 cells XREF_BIBR, suggesting that CARP is a pro apoptotic protein and has potential anti-tumor effects.
MINDY3 affects Cyclin_E
| 1
Modified MINDY3 decreases the amount of Cyclin_E. 1 / 1
| 1

reach
In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21.
| 1

reach
CARP gene silencing inhibits tumor cell survival and increases cancer cell sensitivity to the death ligand or chemotherapy induced apoptosis.
MINDY3 affects CASP8
| 1
MINDY3 inhibits CASP8. 1 / 1
| 1

reach
Additional intracellular factors leading to TRAIL-resistance affect the caspase 8/c-FLIP ratio, such as loss of caspase 8 and caspase 10 due to mutations or gene methylation, CARP dependent degradation of active caspase 8 and changes in caspase 8 or c-FLIP expression levels.
MEIS1 affects MINDY3
1 |
MEIS1 decreases the amount of MINDY3. 1 / 1
1 |

biopax:msigdb
No evidence text available
K 7174 affects MINDY3
1 |
K 7174 increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
ELK1 affects MINDY3
1 |
ELK1 decreases the amount of MINDY3. 1 / 1
1 |

biopax:msigdb
No evidence text available
CHAT affects MINDY3
| 1
CHAT activates MINDY3. 1 / 1
| 1

reach
Mahoney Virus in PFU CHAT Virus in PFU produced at 40 1 113 113 113 113 113 113 113 02 203 203 203 203 203 203 0 3 X 102 3 X 103 104 3 X 104 105 3 X 105 3 X 1050 2 X 108 6 X 103 2 X 104 6 X 104 2 X 10[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
1 |

ctd
No evidence text available
2-hydroxypropanoic acid decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
17alpha-ethynylestradiol decreases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
1-naphthyl isothiocyanate increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
4,4'-sulfonyldiphenol increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available
4,4'-diaminodiphenylmethane increases the amount of MINDY3. 1 / 1
1 |

ctd
No evidence text available