MYSM1 Data Analysis

HGNC Gene Name
Myb like, SWIRM and MPN domains 1
HGNC Gene Symbol
MYSM1
Identifiers
hgnc:29401 NCBIGene:114803 uniprot:Q5VVJ2
Orthologs
mgi:2444584 rgd:1311787
INDRA Statements
deubiquitinations all statements
Pathway Commons
Search for MYSM1
Number of Papers
61 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 MYSM1using 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 MYSM1 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
MYSM1 deubiquitinates His2A. 2 / 2
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In contrast, there was no apparent difference in ubH2A in EBF1 promoter desert region (PDR) and exon 2 regions, as well as in the osteocalcin (OC) promoter locus of WT and Mysm1 -/- Lin - progenitors, suggesting the selective deubiquitination of uH2A at the Ebf1 locus by MYSM1.

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Significantly, although cells were treated with DHT as usual, the amount of pS5-Pol II on the promoter was reduced upon loss of 2A-DUB and increased levels of uH2A, which argues that 2A-DUB and result[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 deubiquitinates H2AC17. 1 / 1
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Review
MYSM1 deubiquitinates H2AC20. 1 / 1
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Myb-Like, SWIRM, and MPN domains 1 (MYSM1) is a metalloprotease that deubiquitinates the K119-monoubiquitinated form of histone 2A (H2A), a chromatin marker associated with gene transcription silencing.

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
TP53 affects MYSM1
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TP53 activates MYSM1. 10 / 11
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As increased p19 ARF / p53 activation in developing Mysm1 deficient mice could be a consequence of checkpoint activation, a default pathway, or be induced as a result of a lack of 2A-DUB/Mysm1 action in regulatory complexes involved in repression of the Cdkn2a (Ink4 and Arf) locus, we next set out to explore Mysm1 binding to fragments of the p19 ARF promoter in activated thymocytes.

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As induction of Cdkn2a and p19 ARF was previously implicated in p53 activation in Mysm1 -/- thymocytes, 39 we conclude that the mechanisms of p53 activation in Mysm1 deficient HSPCs are distinct and p19 ARF -independent.

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However, the mechanisms triggering p53 activation in Mysm1 -/- HSPCs, and the pathways downstream of p53 driving different aspects of the Mysm1 -/- phenotype remain unknown.

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Using double-knockout mouse models, we establish that PUMA, but not p21, is an important mediator of p53 driven Mysm1 -/- hematopoietic dysfunction.

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Our study also provides important insights into the unique effects of p53 stress responses in HSCs, where p53 activation in Mysm1 deficiency does not result in apoptosis, but promotes loss of quiescence.

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To our knowledge, the role of p53 activation in Mysm1 deficient NK cell dysfunction has not been addressed [XREF_BIBR, XREF_BIBR, XREF_BIBR].

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The suggested triggers for p53 activation in Mysm1 -/- include the putative roles of MYSM1 in the maintenance of p19ARF expression within the thymus [XREF_BIBR], and IRF2 and IRF8 expression in bone marrow progenitor cells [XREF_BIBR].

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XREF_BIBR, XREF_BIBR Importantly, Cdkn2a expression was undetectable in Mysm1 deficient HSPCs or MPPs, demonstrating the distinct mechanism of p53 activation in Mysm1 -/- HSPCs, as compared with thymocytes.

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P53 mediates loss of hematopoietic stem cell function and lymphopenia in Mysm1 deficiency.

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In summary, our results demonstrate novel roles for Mysm1 in osteoblast differentiation and osteoclast formation, resulting in osteopenia in Mysm1 deficient mice that could be abrogated by the loss of p53 from increased osteogenic differentiation of Mysm1 -/- p53 -/- MSCs.-Haffner-Luntzer, M., Kovtun, A., Fischer, V., Prystaz, K., Hainzl, A., Kroeger, C. M., Krikki, I., Brinker, T. J., Ignatius, A., Gatzka, M. Loss of p53 compensates osteopenia in murine Mysm1 deficiency.
Modified TP53 activates MYSM1. 1 / 1
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36 Here, we observed enhanced p53 levels in Poly (I : C)-treated mice that paralleled increases in Mysm1 expression, and that there was enhanced p53 transcription in Mysm1 -/- HSCs.
MYSM1 affects TP53
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MYSM1 inhibits TP53.
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MYSM1 inhibits TP53. 4 / 4
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As Mysm1 generally functions as a transcription activator, it is rational to postulate that Mysm1 suppresses p53 or p19 ARF likely by activating expression of transcription repressors.

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Mysm1-deficiency is known to result in p53-activation in hematopoietic cells [ 19,44,45 ] , indicating that MYSM1 normally represses p53 activation , and suggesting it as a possible target for therapeutic p53-activation in hematological malignancies that retain wild type p53 function .

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53 Our work shows that MYSM1 represses p53 stress response genes by antagonizing other histone modifications (H3K27ac and H3K4me3).

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Mysm1-deficiency is known to result in p53 activation in hematopoietic cells [XREF_BIBR, XREF_BIBR, XREF_BIBR], indicating that MYSM1 normally represses p53 activation, and suggesting it as a possible target for therapeutic p53 activation in hematological malignancies that retain wild type p53 function.
MYSM1 increases the amount of TP53.
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MYSM1 increases the amount of TP53. 3 / 3
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To investigate the underlying mechanisms, we first confirmed that Mysm1 -/- mice had enhanced p53 levels in the Lin - HSCs and LSKs as determined by ICS assays (XREF_FIG).

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Further studies revealed that Mysm1 suppressed p53-target gene Bbc3 and PUMA for HSC maintenance 49 and Mysm1 -/- enhanced p53 levels by upregulation of p19 ARF.

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Nijnik et al. 15 demonstrated that Mysm1 -/- mice have enhanced levels of p53, which is a central regulator of cellular stress responses.
MYSM1 decreases the amount of TP53.
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MYSM1 decreases the amount of TP53. 2 / 2
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Our work demonstrates that MYSM1 represses p53 stress response gene expression by localizing to p53 binding sites within Bbc3 and PUMA and Cdkn1a and p21 promoters and antagonizing local histone modification (H3K27ac and H3K4me3) and p53 recruitment (XREF_FIG).

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IRF2 and IRF8 reduction in Mysm1 -/- HSCs enhances p53 levels.
MYSM1 activates TP53.
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MYSM1 activates TP53. 2 / 2
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We recently demonstrated that all developmental and hematopoietic phenotypes of Mysm1 deficiency are p53 mediated and rescued in the Mysm1 -/- p53 -/- mouse model.

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Furthermore, we identify potential mediators of p53 dependent but PUMA independent Mysm1 -/- hematopoietic deficiency phenotypes.

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Further, we tested the possibility that MYSM1 may directly activate the transcription of Pax5 in mature B cells as well.

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The histone H2A deubiquitinase 2A-DUB or Mysm1/Kiaa1915 (Myb-like SWIRM and MPN domain containing1) is a nuclear protein of 828 amino acids containing a SWIRM domain, a SANT (SWI-SNF, ADA N-CoR, TFIIIB) domain with DNA-binding activity and a JAMN/MPN domain with intrinsic metalloprotease-like activity. xref In prostate cancer cells, Mysm1 activates transcription of androgen receptor-regulated genes as part of a co-regulatory complex with histone acetyltransferase p300/CBP-associated factor by coordinating histone acetylation and deubiquitination, and by destabilizing the association of linker histone H1 with nucleosomes. xref More recently, analysis of Mysm1 knockout mice revealed additional functions of the H2A-DUB in regulation of hematopoietic development as Mysm1 deficiency resulted in – among other abnormalities – severe depletion of B cells and T cells, anemia, and thrombocytosis. xref , xref Comparable with the pathophysiology of mice lacking PRC1 component Bmi1, xref postnatal lymphopenia in Mysm1-deficient mice correlated with a depletion of HSC likely resulting from activation of the DDR and uncontrolled production of reactive oxygen species (ROS). xref In murine skin, Mysm1 deficiency was associated with atrophy (present article and own unpublished observations) and malformation of the tail. xref

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MYSM1 stimulates transcription of miR-150 in B1a cells with c-Myc.

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MYSM1 and USP16 activate transcription.

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MYSM1 deubiquitinates monoubiquitinated histone H2A and directs the recruitment of transcription factors to the promoter of target genes, including EBF1 and PU.1.

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An interesting area of future studies is to systemically identify MYSM1 partners and investigate the underlying molecular mechanisms for the selective gene targeting and transcription regulation by MYSM1.

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Mechanistic studies revealed that MYSM1 activates Pax5 transcription by coordinating histone modifications and directing the recruitment of the transcription activators such as PU.1 to the Pax5 locus in B cells.

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MYSM1 reverses the transcription repression of genes that are involved in hematopoietic stem cell homeostasis, hematopoiesis, and lymphocyte differentiation (94).
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MYSM1 reverses the transcription repression of genes that are involved in hematopoietic stem cell homeostasis , hematopoiesis , and lymphocyte differentiation ( 94 ) .
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We demonstrated that MYSM1 intrinsically represses plasma cell differentiation and antibody production.

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MYSM1 negatively regulates differentiation of human B cells to plasma cells.

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We revealed that MYSM1 intrinsically represses plasma cell differentiation and antibody production.

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Mechanistic studies revealed that MYSM1 intrinsically represses plasma cell differentiation and antibody production by activating the transcription of Pax5, the repressors of plasma cell differentiation, in mature B cells.

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MYSM1 intrinsically represses plasma cell differentiation.

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Taken together, these data demonstrate that MYSM1 is an intrinsic repressor of plasma cell differentiation.

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Thus, these data demonstrate that MYSM1 represses plasma cell differentiation, as well as Ig production by plasma cells.
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XREF_FIG shows that forced expression of MYSM1, but not control, rescued the enhanced plasma cell differentiation of Mysm1 -/- B cells.
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MYSM1 silencing decreases migration and invasion in CRC SW480 cells.

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Transwell assay and Scratch assay indicated that MYSM1 silencing markedly inhibited cellular invasion and migration in SW480 cells (XREF_FIG).

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Scratch assay and Transwell assay showed that MYSM1 silencing decreased migration and invasion abilities of SW480 cells.

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In the present study, we knocked down MYSM1 expression by transfecting siRNA for MYSM1 to CRC SW480 cells and found that MYSM1 silencing inhibited the migration and invasion of CRC cells, indicating that MYSM1 expression was positively associated with cell migration and invasion, which was identical to the clinicopathologic characteristics.

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It was found that MYSM-1 could suppress the proliferation, migration, and invasion of renal carcinoma cells.

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These data exhibited the correlation between MYSM1 and CRC malignancy involving cell metastasis ability but not cell proliferation ability.However, it has been reported that MYSM1 suppressed cellular migration and invasion in renal carcinoma by inhibiting epithelial-mesenchymal transition [XREF_BIBR].

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MYSM-1 suppresses migration and invasion in renal carcinoma through inhibiting epithelial-mesenchymal transition.

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Survival and proliferation of melanoma cells is supported by MYSM1.

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Knockdown of MYSM1 promoted cell proliferation and suppressed senescence of CRPC cells under condition of androgen ablation.

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Mysm1 -/- mice had enhanced HSC proliferation that led to a large dysfunctional LSK population.

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In a separate study, Mysm1 -/- macrophages were confirmed to have elevated production of pro inflammatory cytokines in response to stimulation, as well as increased proliferation, increased apoptosis, and enhanced capacity to control melanoma tumor growth in vivo in mouse models [XREF_BIBR].

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It was found that MYSM-1 could suppress the proliferation, migration, and invasion of renal carcinoma cells.

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In conclusion, we reveal a novel pathway involving MYSM1, miR-150, and FLT3, which inhibits B1a cell proliferation and a defect in this pathway may contribute to the pathogenesis of SLE.
MYSM1 affects PAX5
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MYSM1 activates PAX5.
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MYSM1 activates PAX5. 2 / 2
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Mechanistic studies revealed that MYSM1 is a transcriptional activator of Pax5, the repressors of plasma cell differentiation, by facilitating key transcriptional factor recruitment and coordinating histone modifications at the Pax5 locus in B cells.

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Mechanistic studies demonstrated that MYSM1 is a transcriptional activator of Pax5, the repressors of plasma cell differentiation, by facilitating key transcriptional factor recruitment and coordinating histone modifications at the Pax5 loci.
Modified MYSM1 activates PAX5. 1 / 1
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MYSM1 expression activated transcription of the Ebf1alpha promoter and modestly activated the Ebf1beta promoter, but only marginally activated the Pax5 promoter and Cd79a promoter.
MYSM1 increases the amount of PAX5.
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MYSM1 increases the amount of PAX5. 2 / 2
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Further, we tested the possibility that MYSM1 may directly activate the transcription of Pax5 in mature B cells as well.

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Mechanistic studies revealed that MYSM1 activates Pax5 transcription by coordinating histone modifications and directing the recruitment of the transcription activators such as PU.1 to the Pax5 locus in B cells.
MYSM1 decreases the amount of PAX5.
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MYSM1 decreases the amount of PAX5. 1 / 1
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Altogether, MYSM1 was proposed to inhibit plasma cell differentiation by maintaining Pax5 expression, via histone H2AK119 deubiquitination and recruitment of transcription factor PU.1 to the Pax5 locus [XREF_BIBR] (XREF_FIG).

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MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS STING Pathway.

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Thus, MYSM1 is a critical repressor of innate immunity and autoimmunity and is thus a potential therapeutic agent for infectious, inflammatory, and autoimmune diseases.

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This study identifies a distinct mechanism by which MYSM1 suppresses innate immunity and autoimmunity.

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MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway .
MYSM1 affects AR
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MYSM1 increases the amount of AR. 4 / 4
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27 In prostate cancer cells, Mysm1 activates transcription of androgen receptor regulated genes as part of a co and regulatory complex with histone acetyltransferase p300 and CBP associated factor by coordinating histone acetylation and deubiquitination, and by destabilizing the association of linker histone H1 with nucleosomes.

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2A-DUB, a JAMM family DUB, was found to deubiquitinate H2A and positively regulate transcription of androgen receptor regulated genes in concert with the histone acetylase p and CAF complex [XREF_BIBR].

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MYSM-1 can activate transcription of AR target genes via its involvement with p300 affecting histone acetylation and deubiquitination and binding of H1 to the nucleosome [XREF_BIBR].

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Recent work has shown that 2A-DUB acts as a co-activator of the androgen receptor (AR), modulating full activation of AR dependent gene expression through deubiquitination of H2A.
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Hsa-miR-8485 decreases the amount of MYSM1. 3 / 3
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MYSM1 affects Ig
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MYSM1 inhibits Ig. 3 / 3
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MYSM1 intrinsically represses Ig production by plasma cells.

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To investigate the mechanism by which MYSM1 represses plasma cell generation and Ig production, we first examined the expression of a set of transcriptional factors that are critical for plasma cell generation and Ig production XREF_BIBR XREF_BIBR XREF_BIBR by qRT-PCR assays.

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Thus, these data demonstrate that MYSM1 represses plasma cell differentiation, as well as Ig production by plasma cells.
BBC3 affects MYSM1
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BBC3 activates MYSM1. 3 / 3
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XREF_BIBR, XREF_BIBR PUMA drives MPP cell depletion in Mysm1 deficiency.

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The downregulation of cell-cycle progression genes, together with the upregulation of p53 effectors in Mysm1 −/− Puma −/− MPPs further supports persistent stress-response activation in these cells.

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Considering that Mysm1 -/- p53 -/- mice displayed complete rescue of hematopoietic dysfunction, 38 the other p53 effectors identified in our Mysm1 -/- Puma -/- transcriptome analysis may contribute to the PUMA independent but p53 dependent Mysm1 -/- phenotypes.
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Benzo[a]pyrene decreases the amount of MYSM1.
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Benzo[a]pyrene decreases the amount of MYSM1. 2 / 2
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Benzo[a]pyrene increases the amount of MYSM1.
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Benzo[a]pyrene increases the amount of MYSM1. 1 / 1
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MYSM1 affects hemopoiesis
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MYSM1 inhibits hemopoiesis.
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In addition, disorders mainly characterized by B alymphocytosis, T lymphopenia, and hematopoiesis impairment caused by MYSM1 deficiency were found in human subjects XREF_BIBR XREF_BIBR.

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Additionally, the lower representation of reverted circulating T cells might reflect a longer lifespan of the cells already present before the reversion compared with the other cell types analyzed.Our[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 activates hemopoiesis.
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Assuming that the reversion mutation originated in a single HSC, we can conclude that restoration of MYSM1 function provided a very strong selective advantage and allowed one HSC clone to reconstitute normal wild-type hematopoiesis in competition with a large pool of MYSM1 deficient stem and progenitor cells.
MYSM1 affects MYSM1
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MYSM1 activates MYSM1.
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MYSM1 activates MYSM1. 2 / 2
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Loss of Mysm1 Causes Skin Atrophy and Reduced Skin Cellularity in Mysm1 Deficient Mice.

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XREF_FIG shows that forced expression of MYSM1, but not control, rescued the enhanced plasma cell differentiation of Mysm1 -/- B cells.
MYSM1 decreases the amount of MYSM1.
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MYSM1 decreases the amount of MYSM1. 1 / 1
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Western blot analysis showed that MYSM1 siRNA significantly reduced the expression of MYSM1 protein compared with siRNA non transfected or control siRNA transfected SW480 cells (XREF_FIG).
MYSM1 affects IRF8
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MYSM1 activates IRF8.
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MYSM1 activates IRF8. 2 / 2
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We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1 -/- HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis.

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The results showed that Mysm1 significantly enhances IRF2 and IRF8 promoter activity (-600 to +50) (XREF_SUPPLEMENTARY).
MYSM1 decreases the amount of IRF8.
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MYSM1 decreases the amount of IRF8. 1 / 1
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Mysm1 deficiency reduces IRF2 and IRF8 expression in HSCs.
MYSM1 affects IRF2
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MYSM1 activates IRF2.
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MYSM1 activates IRF2. 2 / 2
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The results showed that Mysm1 significantly enhances IRF2 and IRF8 promoter activity (-600 to +50) (XREF_SUPPLEMENTARY).

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We found that IRF2 and IRF8, which are important for HSC homeostasis and commitment as transcription repressors, were expressed at lower levels in Mysm1 -/- HSCs, and Mysm1 enhanced function of the IRF2 and IRF8 promoters, suggesting that Mysm1 governs the IRFs for HSC homeostasis.
MYSM1 decreases the amount of IRF2.
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MYSM1 decreases the amount of IRF2. 1 / 1
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Mysm1 deficiency reduces IRF2 and IRF8 expression in HSCs.
Tamoxifen affects MYSM1
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Mysm1 flox and flox line was generated by crossing Mysm1 tm1a mice to the Gt (ROSA) 26 Sor tm1 (FLP1) Dym and Wtsi line with ubiquitous expression of Flp recombinase, 56 and subsequently bred to Gt (ROSA) 26Sor tm1 (cre and ERT2) mice for tamoxifen induced Mysm1 inactivation.

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For tamoxifen induced Mysm1 gene inactivation in the Mysm1 flox and flox Gt (ROSA) 26Sor tm1 (cre and ERT2) mouse line, the mice were injected intraperitoneally with tamoxifen (T5648, Sigma, St. Louis, MO, USA) in sterilized corn oil (Sigma C8267) at 0.15 mg/g per injection, with eight doses in total administered over 16 days.
Bisphenol A affects MYSM1
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Bisphenol A decreases the amount of MYSM1. 2 / 2
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MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.

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Furthermore, silencing MYSM1 stimulated PI3K/AKT signaling and promoted EMT in CRC cells.

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Knockdown of MYSM1 promoted cell proliferation and suppressed senescence of CRPC cells under condition of androgen ablation.

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MYSM1 functionally represses cellular senescence and the aging process in human and mice primary cells and in mice organs.
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33 Using Ki67 as a marker of non quiescent cells, we show that Mysm1 -/- HSC loss of quiescence is rescued in Mysm1 -/- p53 -/- HSCs (XREF_FIG, right).

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Overall, this suggests that continued dysregulation of p53 effector functions beyond the upregulation of Bbc3 and PUMA contributes to persistent Mysm1 -/- HSC loss of quiescence, and also to the lymphoid differentiation arrest of Mysm1 -/- Puma -/- MPP4s.
MYSM1 affects PI3K
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MYSM1 inhibits PI3K. 2 / 2
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MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.

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Furthermore, silencing MYSM1 stimulated PI3K/AKT signaling and promoted EMT in CRC cells.
EBF1 affects MYSM1
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EBF1 increases the amount of MYSM1. 2 / 2
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We identified the transcription factor EBF1 as a pivotal target gene of MYSM1 in lymphoid precursors and demonstrated that MYSM1 epigenetically de-represses EBF1 transcription by orchestrating histone modifications and regulating recruitment of the transcription factors to the EBF1 locus.

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In an attempt to investigate how MYSM1 activates Ebf1 transcription, we first determined whether MYSM1 deubiquitinates ubH2A at the Ebf1 promoter locus of B-cell precursors.
PAX5 affects MYSM1
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PAX5 increases the amount of MYSM1.
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PAX5 increases the amount of MYSM1. 1 / 1
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Mechanistic studies revealed that MYSM1 activates Pax5 transcription by coordinating histone modifications and directing the recruitment of the transcription activators such as PU.1 to the Pax5 locus in B cells.
PAX5 activates MYSM1.
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PAX5 activates MYSM1. 1 / 1
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XREF_FIG shows that mRNA levels of Pax5 and Bach2 were significantly reduced, while Blimp1 and Xbp1 mRNA levels were significantly elevated in naive and activated Mysm1 -/- B cells.
MYSM1 affects EBF1
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MYSM1 increases the amount of EBF1.
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MYSM1 increases the amount of EBF1. 1 / 1
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In an attempt to investigate how MYSM1 activates Ebf1 transcription, we first determined whether MYSM1 deubiquitinates ubH2A at the Ebf1 promoter locus of B-cell precursors.
MYSM1 activates EBF1.
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MYSM1 activates EBF1. 1 / 1
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BRM or BRG-1 silencing reduced MYSM1 mediated Ebf1 promoter transcription (XREF_SUPPLEMENTARY).
MYSM1 affects CDH1
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MYSM1 inhibits CDH1.
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MYSM1 inhibits CDH1. 1 / 1
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MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.
MYSM1 decreases the amount of CDH1.
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MYSM1 decreases the amount of CDH1. 1 / 1
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Mechanistically, MYSM1 directly bound to the promoter region of miR-200/CDH1, impaired the enrichment of repressive H2AK119ub1 modification and epigenetically enhanced miR-200/CDH1 expression.
Vincristine affects MYSM1
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Vincristine increases the amount of MYSM1. 1 / 1
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Valproic acid decreases the amount of MYSM1. 1 / 1
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Tungsten affects MYSM1
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Tungsten decreases the amount of MYSM1. 1 / 1
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Troglitazone decreases the amount of MYSM1. 1 / 1
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Thapsigargin increases the amount of MYSM1. 1 / 1
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Testosterone undecanoate decreases the amount of MYSM1. 1 / 1
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Sunitinib affects MYSM1
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Sunitinib increases the amount of MYSM1. 1 / 1
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Sulforaphane decreases the amount of MYSM1. 1 / 1
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Sodium arsenate increases the amount of MYSM1. 1 / 1
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Propiconazole decreases the amount of MYSM1. 1 / 1
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Progesterone decreases the amount of MYSM1. 1 / 1
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Potassium chromate increases the amount of MYSM1. 1 / 1
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Miconazole affects MYSM1
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Miconazole decreases the amount of MYSM1. 1 / 1
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Methyl methanesulfonate increases the amount of MYSM1. 1 / 1
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Levonorgestrel decreases the amount of MYSM1. 1 / 1
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Jinfukang affects MYSM1
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Jinfukang decreases the amount of MYSM1. 1 / 1
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Irinotecan affects MYSM1
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Irinotecan decreases the amount of MYSM1. 1 / 1
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Hsa-miR-484 affects MYSM1
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Hsa-miR-484 decreases the amount of MYSM1. 1 / 1
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Hsa-miR-376b-3p decreases the amount of MYSM1. 1 / 1
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Hsa-miR-376a-3p decreases the amount of MYSM1. 1 / 1
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biopax:mirtarbase
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Hsa-miR-186-5p decreases the amount of MYSM1. 1 / 1
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biopax:mirtarbase
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Formaldehyde increases the amount of MYSM1. 1 / 1
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ctd
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Endosulfan affects MYSM1
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Endosulfan increases the amount of MYSM1. 1 / 1
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ctd
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Doxorubicin affects MYSM1
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Doxorubicin decreases the amount of MYSM1. 1 / 1
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ctd
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Dichloromethane decreases the amount of MYSM1. 1 / 1
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ctd
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Diazinon affects MYSM1
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Diazinon increases the amount of MYSM1. 1 / 1
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ctd
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Cerium trichloride increases the amount of MYSM1. 1 / 1
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ctd
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Carbon nanotube decreases the amount of MYSM1. 1 / 1
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ctd
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Bis(2-chloroethyl) sulfide decreases the amount of MYSM1. 1 / 1
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ctd
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Acetylsalicylic acid decreases the amount of MYSM1. 1 / 1
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Aspirin administration, reduced the protein expression of Mysm1, increased the protein expression of H2AK119-Ub and thereby reduced the Set7 protein expression in glomeruli isolated from diabetic animals and prevented renal fibrosis.
Abrine affects MYSM1
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Abrine increases the amount of MYSM1. 1 / 1
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ctd
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TP63 affects MYSM1
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TP63 increases the amount of MYSM1. 1 / 1
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Alternatively, Mysm1 may influence p63 transcription by counteracting chromatin changes induced by PRC1 component Bmi1 -- with context dependent activatory or inhibitory influence in stem cells [XREF_BIBR], [and unpublished meeting communications].

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53 Our work shows that MYSM1 represses p53 stress response genes by antagonizing other histone modifications (H3K27ac and H3K4me3).

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Altogether , MYSM1 was proposed to inhibit plasma cell differentiation by maintaining Pax5 expression , via histone H2AK119-deubiquitination and recruitment of transcription factor PU.1 to the Pax5 locus [ 30 ] ( Figure 2 ) .
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Furthermore, Mysm1 deficient cells transduced with lentivirus containing miR-150 mimics produced less pro inflammatory factors and more NO.

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Strong IL-15 receptor stimulation by IL-2 pre-ligated to an anti-IL-2 antibody, or SOCS-3 deficiency, partially restores homeostasis in Id2 deficient NK cells.In support of the role of ID2 in NK cell maturation, deficiency of MYSM1, which mediates the recruitment of E4BP4 to the Id2 locus, leads to defects in NK cell maturation, but not NK lineage specification or commitment (23).

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Furthermore, silencing MYSM1 stimulated PI3K/AKT signaling and promoted EMT in CRC cells.
MYSM1 affects dioxygen
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The Mysm1 -/- thymocytes also produced enhanced levels of reactive oxygen species (ROS), but reduced the mitochondrial membrane potential (XREF_FIG).
MYSM1 affects cell death
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To gain insight into the functional defects in Mysm1 -/- Puma -/- MPP4s contributing to cell death and downstream lymphopoiesis failures, we performed RNA sequencing (RNA-Seq) of MPPs (Lin - cKit + Sca1 + CD150 -) from Mysm1 -/- Puma -/-, Mysm1 -/- Puma +/-, Puma -/-, and wild-type mice (Mysm1 -/- Puma +/- phenocopies Mysm1 -/-).
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In addition, another study confirmed that the deletion MYSM1 restores dormant HSCs to a cyclic state and enhances apoptosis of HSCs, leading to depletion in the stem cell pool through blocked recruitment of the transcription factors GATA2 and RUNX1 to the GFI1 locus [XREF_BIBR].
MYSM1 affects XBP1
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MYSM1 activates XBP1. 1 / 1
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Furthermore, Mysm1 -/- plasma cells showed enhanced levels of antibody secretion in vitro and had altered gene expression profiles with downregulation of B cell lineage transcription factors Pax5 and Bach2, and increased expression of plasma cell transcription factors Blimp1 and Xbp1 [XREF_BIBR].
MYSM1 affects THR
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MYSM1 increases the amount of THR. 1 / 1
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In contrast, RARbeta2, a known target gene of retinoic acid receptor alpha (RARalpha), was not detectably regulated by 2A-DUB, and thyroid hormone receptor (T 3 R)-mediated transcription was repressed[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects RUNX1
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MYSM1 activates RUNX1. 1 / 1
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Loss of MYSM1 was associated with increased H2AK119Ub levels, increased recruitment of PRC1 components Ring1B and Bmi1, and reduced binding of hematopoietic transcription factors Gata2 and Runx1 to th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects RNF2
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MYSM1 inhibits RNF2. 1 / 1
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Loss of MYSM1 was associated with increased H2AK119Ub levels, increased recruitment of PRC1 components Ring1B and Bmi1, and reduced binding of hematopoietic transcription factors Gata2 and Runx1 to th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects PRDM1
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MYSM1 activates PRDM1. 1 / 1
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Furthermore, Mysm1 -/- plasma cells showed enhanced levels of antibody secretion in vitro and had altered gene expression profiles with downregulation of B cell lineage transcription factors Pax5 and Bach2, and increased expression of plasma cell transcription factors Blimp1 and Xbp1 [XREF_BIBR].
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The authors concluded that MYSM1 antagonizes the action of the polycomb repressive complex 1 (PRC1) on the Ebf1 promoter, enabling lineage specific transcription factors, such as E2A, to be recruited to the Ebf1 locus and to induce its transcription [XREF_BIBR].

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Therefore, we hypothesized that MYSM-1 may suppress the metastasis of renal cell carcinoma in light of paucity of data regarding MYSM-1 in the cancers.
MYSM1 affects NOS2
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MYSM1 activates NOS2. 1 / 1
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Mysm1, a histone deubiquitinase, is induced by TNF-alpha and IFNgamma in ASCs and promotes miR-150 transcription, which enhances iNOS production.

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The Mysm1 -/- thymocytes also produced enhanced levels of reactive oxygen species (ROS), but reduced the mitochondrial membrane potential (XREF_FIG).
MYSM1 affects MYC
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MYSM1 activates MYC. 1 / 1
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Loss of MYSM1 inhibits the oncogenic activity of cMYC in B cell lymphoma.
MYSM1 affects MEK
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MYSM1 inhibits MEK. 1 / 1
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Significant reduction of MYSM1 protein expression was detectable upon treatment of A375 cells with either inhibitor PD128,345, targeting mitogen activated protein kinase kinase MEK, alone or in combination with an Akt1/2-inhibitor for 24 hrs.
MYSM1 affects MAPK
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MYSM1 inhibits MAPK. 1 / 1
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Significant reduction of MYSM1 protein expression was detectable upon treatment of A375 cells with either inhibitor PD128,345, targeting mitogen activated protein kinase kinase MEK, alone or in combination with an Akt1/2-inhibitor for 24 hrs.
MYSM1 affects Leu-Lys
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We found that MYSM1 deficiency significantly reduced the proportion of LSK cells and LK cells in the G 0 phase, whereas there was a significant increase in the proportion of LSK cells and LK cells in G 1 phase (XREF_FIG).
MYSM1 affects Histone
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53 Our work shows that MYSM1 represses p53 stress response genes by antagonizing other histone modifications (H3K27ac and H3K4me3).
MYSM1 affects His2A
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MYSM1 decreases the amount of His2A. 1 / 1
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WT 2A-DUB substantially decreased uH2A levels, whereas the D567N mutant, in which the key aspartic acid residue required for the metal-binding-dependent deubiquitinase activity was substituted to a no[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects GATA2
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MYSM1 activates GATA2. 1 / 1
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Loss of MYSM1 was associated with increased H2AK119Ub levels, increased recruitment of PRC1 components Ring1B and Bmi1, and reduced binding of hematopoietic transcription factors Gata2 and Runx1 to th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects FLT3
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Modified MYSM1 decreases the amount of FLT3. 1 / 1
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We then demonstrated that ectopic expression of both miR-150 and MYSM1 in MYSM1 -/- B1a cells reduced the level of FLT3.
MYSM1 affects DPEP1
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MYSM1 inhibits DPEP1. 1 / 1
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118 Expression of MYSM1 decreases MDP stimulated NOD2 activation in cells, and in mouse models, knockout of MYSM1 leads to increased inflammation and liver damage, showing the DUB to be a critical negative regulator of NOD2 signaling.
MYSM1 affects DNA repair
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MYSM1 mechanistically attenuates the aging process by promoting DNA repair processes.
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MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.
MYSM1 affects CLPS
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MYSM1 inhibits CLPS. 1 / 1
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We further establish that PUMA, but not p21, is an important mediator of the p53 driven hematopoietic dysfunction in Mysm1 deficiency, with Mysm1 -/- Puma -/- mice showing full rescue of MPP4 cell viability, partial rescue of HSC functions, but persistent depletion of CLPs and lymphopenia.
MYSM1 affects CDKN2A
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MYSM1 inhibits CDKN2A. 1 / 1
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Lymphoid cell depletion in Mysm1 deficiency was previously attributed to several mechanisms, involving either MYSM1 mediated Cdkn2a and p19 ARF repression to restrict p53 activation in thymocytes, 39 or MYSM1 mediated induction of lymphoid-lineage genes, such as Ebf1 and Id2.
MYSM1 affects CD8
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MYSM1 activates CD8. 1 / 1
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Mysm1 ablation resulted in a twofold reduction in CD8 + T-cell numbers, and also led to a hyperactivated CD8 + T-cell state accompanied by impaired proliferation and increased pro inflammatory cytokine production after ex vivo stimulation.
MYSM1 affects CD79A
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Modified MYSM1 activates CD79A. 1 / 1
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MYSM1 expression activated transcription of the Ebf1alpha promoter and modestly activated the Ebf1beta promoter, but only marginally activated the Pax5 promoter and Cd79a promoter.
MYSM1 affects BMI1
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MYSM1 inhibits BMI1. 1 / 1
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Loss of MYSM1 was associated with increased H2AK119Ub levels, increased recruitment of PRC1 components Ring1B and Bmi1, and reduced binding of hematopoietic transcription factors Gata2 and Runx1 to th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
MYSM1 affects BBC3
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MYSM1 inhibits BBC3. 1 / 1
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Repression of p53-target gene Bbc3 and PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance.
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MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway .
IFNG affects MYSM1
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IFNG activates MYSM1. 1 / 1
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Mysm1 , a histone deubiquitinase , is induced by TNF-alpha and IFNgamma in ASCs and promotes miR-150 transcription , which enhances iNOS production .
His2A affects MYSM1
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His2A activates MYSM1. 1 / 1
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Significantly, although cells were treated with DHT as usual, the amount of pS5-Pol II on the promoter was reduced upon loss of 2A-DUB and increased levels of uH2A, which argues that 2A-DUB and result[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]
DEGs affects MYSM1
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DEGs inhibits MYSM1. 1 / 1
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DEGs involved in epigenetic regulation include upregulatd NSD1 and downregulated KDM5A and MYSM1 (XREF_SUPPLEMENTARY).
BACH2 affects MYSM1
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BACH2 activates MYSM1. 1 / 1
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XREF_FIG shows that mRNA levels of Pax5 and Bach2 were significantly reduced, while Blimp1 and Xbp1 mRNA levels were significantly elevated in naive and activated Mysm1 -/- B cells.
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ctd
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17alpha-ethynylestradiol increases the amount of MYSM1. 1 / 1
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ctd
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ctd
No evidence text available