IndraLab
Statements
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"Together, our data showed that BAP1 decreases whereas PRC1 increases H2Aub binding on the SLC7A11 promoter, but both BAP1 and PRC1 represses SLC7A11 expression, thus supporting a model that a balance between H2A ubiquitination and de-ubiquitination might be important for maintaining SLC7A11 repression (see Discussion)."
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"Analysis of our H2Aub ChIP-seq data revealed that restoration of BAP1 WT, but not BAP1 C91A, markedly decreased H2Aub occupancy at both the promoter and gene body of SLC7A11 (XREF_FIG), which was further confirmed by H2Aub ChIP assay on the SLC7A11 promoter and representative exons (XREF_FIG and XREF_SUPPLEMENTARY)."
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"As discussed in Boxes 2 and 3, inactivation of tumour suppressors such as p53, BAP1, kelch-like ECH associated protein 1 (KEAP1) and ARF (p14), or activation of oncogenic KRAS, upregulates SLC7A11 expression, which can be dependent or independent of nuclear factor erythroid 2-related factor 2 (NRF2), conferring ferroptosis evasion and promoting tumour growth ."
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"Given that miR-31-5p has been shown to reduces DOX-induced cardiac toxicity [16], we investigated the role of the targeted relationship between miR-31-5p and BAP1 in SCM.Against this background, it is clear that the regulation of SLC7A11 deubiquitination by BAP1 may have an impact on ferroptosis in SCM."
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"Our data that BAP1 plays a role in regulating several metabolic pathways in osteoclasts also supports this concept.Repression of Slc7a11, the cystine/glutamate xCT amino acid antiporter that antagonizes glutamate metabolism in osteoclasts, is one mechanism by which BAP1 regulates such pathways ."
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"18, NO. 8, 773-783 https://doi.org/10.1080/15384101.2019.1597506EXTRA VIEWRegulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1Yilei Zhang a, Pranavi Koppula a, b, and Boyi Gan a, baDepartment of Experimental Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; bDepartment of Experimental Radiation Oncology, The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences, Houston, TX, USAABSTRACTSLC7A11 (or xCT) imports extracellular cystine into cells to promote glutathione synthesis, thus inhibiting ferroptosis."
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"Cell CycleISSN : 1538-4101 (Print) 1551-4005 (Online) Journal homepage : https://www.tandfonline.com/loi/kccy20Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1Yilei Zhang, Pranavi Koppula & Boyi GanTo cite this article : Yilei Zhang, Pranavi Koppula & Boyi Gan (2019) Regulation of H2A ubiquitination and SLC7A11 expression by BAP1 and PRC1, Cell Cycle, 18:8, 773-783, DOI : 10.1080/15384101.2019.1597506 To link to this article : https://doi.org/10.1080/15384101.2019.1597506View supplementary material Accepted author version posted online : 23 Mar 2019."
sparser
"The proteasome has both ubiquitin ligases and DUBs that associate with it (Crosas et al., 2006) , and several DUB-ligase pairs interact directly, including BRCC36-BRCA1, BAP1-BRCA1, USP4-Ro52, USP7-MDM2, USP8-GRAIL, USP20-pVHL, USP33-pVHL and USP44-APC (Kee and Huibregtse, 2007; Marfany and Denuc, 2008; Ventii and Wilkinson, 2008) ."
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"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15
BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."
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"Their studies revealed differential expression of the cancer-related lncRNAs Malat1, Neat1, H19, Meg3, and their associated miRNA-target pairs, regulating various hallmarks of tumorigenesis such as cell cycle and p53 signaling.BRCA1-Associated Protein 1 (BAP1) is known to enhance BRCA1 tumor suppressor potential and its inactivation is associated with various cancers, in particular clear-cell renal cell carcinoma (ccRCC)."
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"A previous study on the expression of BAP1 tumor suppressor gene in 1222 patients with TCGA breast cancer data reported that the expression of BAP1, which enhances BRCA1-mediated suppression of cell proliferation through BRCA1 stabilization, is highly correlated with USP19 expression."
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"We further found that BAP1 depletion suppressed the assembly of constitutive BRCA1 foci, which are associated with homologous recombination (HR), but had minimal effect on gamma-H2AX foci and did not affect proteins associated with nonhomologous end joining, suggesting that BAP1 affects radiosensitivity in HNSCC by modifying HR."
BAP1 is modified
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"The central region of BAP1 is predicted to be disordered. Sites within this central region have been identified as important for binding non-ASXL complex components; for example, the HCF-binding motif and the phosphorylated threonine residue that mediates BAP1's interaction with FOXK2 have been mapped to this region [96,97]. Additionally, phosphorylation of six sites within this region has been shown to be important for BAP1's role in DNA double-strand break repair [88]."
BAP1 is ubiquitinated.
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BAP1 is methylated.
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BAP1 is glycosylated.
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"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
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"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
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"Tumor suppressors such as p53, BRCA1-associated protein 1 (BAP1), and Kelch-like ECH-associated protein 1 (KEAP1) have been shown to exert their tumor-suppressive functions via inducing ferroptosis.P53 is regarded as the most critical barrier for cancer development by its cell-cycle surveillance function."
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"Therefore, it will be important to investigate the mechanism underlying the tumor-promoting effect of BAP1 inactivation in each cell type.In summary, this study demonstrated that Bap1 loss promotes tumorigenesis only in the tissues in which Bap1 is not engaged in pro-survival gene expression, providing an explanation for the tissue specificity of the BAP1 cancer predisposition syndrome."
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"Cutaneous melanoma, melanocytic tumors and other skin tumors:.
The frequency of cutaneous melanoma (CM) development is likely to increase with germline BAP1 mutations and tumor-promoting effects of these BAP1 mutations are strongly influenced by co-occurrence of associated oncogenes such as mutant BRAF (2,43)."
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"Of note, the BAP1-UCH loop is larger than the ones in other UCH proteins, with a high conservation of both these loop amino acids and of multiple amino acids structurally near this loop ( xref , xref , xref ), implying that larger substrates may be available to BAP1’s catalytic cleavage site than for other UCH domains, yielding a BAP1-specific recruitment of proteins/domains such as ASX and ULD for enzyme regulation ( xref )."
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"In contrast to primary nucleation, secondary nucleation is influenced by local environmental fluctuations and molecular noise, which can lead to variable onset times and heterogeneous spatial distribution of aggregates in cells, as reflected in the variability observed in global fitting of k 2 and n 2 parameters for BAP1‐UCH variants (Table xref and S2, Supporting Information)."
BAP1 affects cell population proliferation
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BAP1 inhibits cell population proliferation.
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"A previous study on the expression of BAP1 tumor suppressor gene in 1222 patients with TCGA breast cancer data reported that the expression of BAP1, which enhances BRCA1-mediated suppression of cell proliferation through BRCA1 stabilization, is highly correlated with USP19 expression."
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BAP1 activates cell population proliferation.
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BAP1 activates cell population proliferation. 10 / 52
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"Therefore, BAP1 might be serve as a potential target for high-risk NB with amplified MYCN.However, Sime et al. found that BAP1 overexpression could also induce apoptosis to retard BE2C cells proliferation by releasing Bax through 14–3–3 protein interaction and reducing the Bcl-2 expression regardless of BAP1 DUB activity [28]."
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"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
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"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
sparser
"The proteasome has both ubiquitin ligases and DUBs that associate with it (Crosas et al., 2006) , and several DUB-ligase pairs interact directly, including BRCC36-BRCA1, BAP1-BRCA1, USP4-Ro52, USP7-MDM2, USP8-GRAIL, USP20-pVHL, USP33-pVHL and USP44-APC (Kee and Huibregtse, 2007; Marfany and Denuc, 2008; Ventii and Wilkinson, 2008) ."
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"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15
BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."
sparser
"ASXL2-BAP1 interactions have been shown to play a role in the suppression of solid tumorigenesis (e.g., human mesotheliomas and lung cancers), and ASXL2-BAP1 complexes, similar to ASXL1-BAP1 complexes, demonstrated to interact with BAP1-interacting proteins (e.g., YY1, FOXK1/2, OGT, and HCF1) [ xref ]."
sparser
"ASXL2-BAP1 interactions have been shown to play a role in the suppression of solid tumorigenesis (e.g., human mesotheliomas and lung cancers), and ASXL2-BAP1 complexes, similar to ASXL1-BAP1 complexes, demonstrated to interact with BAP1-interacting proteins (e.g., YY1, FOXK1/2, OGT, and HCF1) [ xref ]."
BAP1 affects apoptotic process
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BAP1 activates apoptotic process.
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BAP1 activates apoptotic process. 10 / 55
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"Therefore, BAP1 might be serve as a potential target for high-risk NB with amplified MYCN.However, Sime et al. found that BAP1 overexpression could also induce apoptosis to retard BE2C cells proliferation by releasing Bax through 14–3–3 protein interaction and reducing the Bcl-2 expression regardless of BAP1 DUB activity [28]."
BAP1 inhibits apoptotic process.
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BAP1 affects Neoplasm Metastasis
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BAP1 inhibits Neoplasm Metastasis.
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BAP1 inhibits Neoplasm Metastasis. 10 / 31
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"19 However, GNA11 mutations are also more common in tumors involving the ciliary body, which is an independent risk factor for metastasis, and in tumors with mutations in the metastasis suppressor BAP1 (Breast cancer 1, early onset (BRCA1)-associated protein 1) (see below), so it remains possible or even likely that the association between GNA11 and metastasis is not causal."
BAP1 activates Neoplasm Metastasis.
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BAP1 activates Neoplasm Metastasis. 10 / 27
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Mutated BAP1 activates Neoplasm Metastasis. 4 / 4
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"For instance, BAP1 deubiquitinates and stabilizes the transcription factor KLF5, which is highly expressed in breast cancer and a potent biomarker for unfavorable prognosis in breast cancer patients, and promotes breast cancer cell proliferation, survival, and migration as well as tumor growth ."
"<span class="match term0">BAP1</span> interacts directly with <span class="match term1">KLF5</span> and stabilizes <span class="match term1">KLF5</span> via deubiquitination"
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"Notably, KLF5 is de-ubiquitylated by BRCA1 associated protein-1 (BAP1) (Jia et al. 2021; Qin et al. 2015) and suppresses autophagy by activating the PI3K-AKT-mTOR signaling (Jia et al. 2021) that can inhibit the autophagy initiation and the autophagosome formation via modulating the activity of AMBRA1 and ULK1 complex (Xu et al. 2020; Nazio et al. 2013)."
IHC affects BAP1
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IHC inhibits BAP1.
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IHC increases the amount of BAP1.
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"These data are consistent with those of XREF_BIBR) for both patient survival based on the BAP1 mutational status (32 vs 133 months for BAP1 mutation positive vs BAP1 mutation negative tumours) or BAP1 protein expression (31 vs 133 months for tumours showing negative BAP1 expression by IHC vs those with positive BAP1 expression) and thus the proposed role of BAP1 in the pathogenesis of UM with an aggressive phenotype."
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"Our observation that a greater number of tumors exhibited loss of BAP1 protein expression by IHC compared with BAP1 deletions or mutations indicates that BAP1 may become functionally inactivated by mechanisms other than deletions or mutations in the coding region; for example, epigenetic changes leading to silencing of the BAP1 gene or other, yet to be identified, alterations that prevent BAP1 expression."
IHC decreases the amount of BAP1.
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"Recently, loss of BAP1 (BRCA1-associated protein-1) expression by IHC, homozygous deletion of CDKN2A (p16) by FISH, and expression of methyl-thio-adenosine phosphorylase (MTAP) by IHC were added as markers to distinguish non-neoplastic from neoplastic cells when mesothelial proliferation is confined to the serosal surface."
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"Our observation that a greater number of tumors exhibited loss of BAP1 protein expression by IHC compared with BAP1 deletions or mutations indicates that BAP1 may become functionally inactivated by mechanisms other than deletions or mutations in the coding region; for example, epigenetic changes leading to silencing of the BAP1 gene or other, yet to be identified, alterations that prevent BAP1 expression."
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"To investigate whether BAP1 can deubiquitylate and stabilize OGT directly, rather than decreased OGT being secondary to a reduction in HCF-1, we affinity purified ubiquitylated and Myc tagged human OGT from HEK293T cells, and then incubated it with human BAP1 and human ASXL1 residues 2-365 co-purified from Sf9 cells."
"The tumor suppressor <span class="match term0">BAP1</span> associates with ASXL1/2 to form the core Polycomb complex PR-DUB, which catalyzes the removal of mono-ubiquitin from several substrates including histone H2A. This complex also mediates the poly-deubiquitination of HCFC1, <span class="match term1">OGT</span> and PCG1-alpha, preventing them from proteasomal degradation."
BAP1 affects Mesothelioma
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BAP1 activates Mesothelioma.
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BAP1 activates Mesothelioma. 10 / 18
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"On the other hand, the occasionally described heterozygous deletions of these genes cannot be completely excluded in our series, because NGS procedure and mode of data analysis were not sensitive to moderate CNV (copy number variation), the detection of which was not the aim of this panel.Germline mutations in BAP1 are known to underlie sometimes melanomas, renal cell carcinomas, malignant mesotheliomas, and some other cancers [31]."
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"The data show that the top 2 mutant genes in both groups are BAP1 and NF2, which is consistent with the conclusion that the inactivation of BAP1 with loss of NF2 or CDKN2A promotes the development of malignant mesothelioma in approximately 20% of mice with double conditional knockout (CKO), as already reported in the previous literature."
Mutated BAP1 activates Mesothelioma. 7 / 7
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BAP1 inhibits Mesothelioma.
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BAP1 inhibits Mesothelioma. 10 / 22
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"Loss of BAP1 and MTAP can support the diagnosis of mesothelioma versus benign mesothelial proliferation: however, morphology (with an invasive pattern) is still the essential tool to distinguish malignant from benign disease.Molecular analyses: FISH for alterations in CDKN2A and NF2 (as IHC for BAP1 and MTAP) can be used to support the diagnosis of mesothelioma versus benign mesothelial proliferation."
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"We previously validated IHC assays with Sanger sequencing to evaluate PBRM1 and BAP1 protein expression in which negative nuclear staining associates with PBRM1 and BAP1 mutations. xref , xref We used background stroma and lymphocyte nuclei as a positive control, and therefore, we excluded from our analysis samples that lacked stroma/lymphocyte nuclear staining, focal negative or weak positive staining in these cells ( xref )."
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"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
BAP1 affects ferroptosis
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BAP1 activates ferroptosis.
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BAP1 inhibits ferroptosis.
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"We previously validated IHC assays with Sanger sequencing to evaluate PBRM1 and BAP1 protein expression in which negative nuclear staining associates with PBRM1 and BAP1 mutations. xref , xref We used background stroma and lymphocyte nuclei as a positive control, and therefore, we excluded from our analysis samples that lacked stroma/lymphocyte nuclear staining, focal negative or weak positive staining in these cells ( xref )."
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"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
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"While ubiquitination enzyme UBE2O monoubiquitinates the NLS of BAP1 and induces translocation (inactivation) of BAP1 from the nucleus to the cytoplasm, DUB activity of the UCH-domain of BAP1 counteracts the UBE2O activity mediated through the intramolecular interaction between the UCH-domain and COOH-terminal domain of BAP1."
BAP1 affects Neoplasm Invasiveness
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BAP1 inhibits Neoplasm Invasiveness.
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BAP1 inhibits Neoplasm Invasiveness. 10 / 21
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"Moreover, both scratching assay and Matrigel invasion assay indicated that overexpression of BAP1 in HCCC9810 cells significantly reduced cell migratory and invasion capacities, while the motility and invasion potential of RBE-shBAP1 cells were evidently enhanced compared to RBE-Mock cells (Fig. 2d, e)."
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"These results indicated that BAP1 suppressed ICC cell proliferation, cell cycle progression, and invasion via inhibiting ERK1/2 and JNK/c-Jun signaling pathways.To further validate these findings, we used inhibitors of the ERK1/2 pathway (U0126) and JNK/c-Jun pathway (SP600125) in RBE-shBAP1 cells."
BAP1 inhibits Neoplasm Invasiveness. 3 / 3
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"Interestingly, recent research has revealed that the gain of chromosomal 8q may worsen prognosis by activating macrophage infiltration, and the loss of BAP1 expression may drive T cell infiltration in UM (Gezgin et al., 2017), suggesting that immune infiltration plays a crucial role in the prognosis of UM.Emerging evidence shows that the immune microenvironment is crucial for cancer progression and response to therapeutics (Quail and Joyce, 2013)."
BAP1 activates Neoplasm Invasiveness.
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BAP1 affects cell death
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BAP1 activates cell death.
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"Although this remains to be investigated, these results, suggest that the majority of BAP1 partners regulate SLC7A11 expression and possibility impact ferroptosis.Because ferroptosis and apoptosis are two distinct programs in BAP1-mediated cell death, it will be worth to investigate whether these processes act in concert or independently during cancer development."
BAP1 inhibits cell death.
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BAP1 inhibits cell death. 10 / 13
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"The group of flg22 induced MPK4 dependent genes encode important regulators of plant defence such as the cell death inhibitor BAP1 [XREF_BIBR], the calcium dependent protein kinase CPK5 [XREF_BIBR], the exocyst complex subunit EXO70B2 [XREF_BIBR], the cyclic nucleotide gated ion channel CNGC11 [XREF_BIBR] or the BAK1 like receptor kinase BKK1 and SERK4 [XREF_BIBR]."
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"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15
BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."
E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
BAP1 affects cell growth
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BAP1 inhibits cell growth.
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BAP1 activates cell growth.
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BAP1 affects H2Aub
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BAP1 deubiquitinates H2Aub.
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BAP1 inhibits H2Aub.
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"Analysis of our H2Aub ChIP-seq data revealed that restoration of BAP1 WT, but not BAP1 C91A, markedly decreased H2Aub occupancy at both the promoter and gene body of SLC7A11 (XREF_FIG), which was further confirmed by H2Aub ChIP assay on the SLC7A11 promoter and representative exons (XREF_FIG and XREF_SUPPLEMENTARY)."
BAP1 decreases the amount of H2Aub.
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"Our analysis showed that BAP1 restoration in control UMRC6 cells decreased H2Aub and SLC7A11 levels to similar degrees to that in NRF2 or ATF4 KO UMRC6 cells, suggesting that BAP1 regulates SLC7A11 expression independent of NRF2 or ATF4.PRC1 regulates SLC7A11 expression and h2aub occupancy on the SLC7A11 promoterSince our study suggested that BAP1 represses SLC7A11 expression through regulating H2Aub CELL CYCLE777Figure 1."
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"As the expression of BAP1, but not its catalytic dead form, is known to reduce the global levels of H2Aub, this strategy has been used to capture genomic locations that exhibit higher levels of H2Aub using chromatin immunoprecipitation in combination with next-generation genome sequencing (ChIP-Seq) ."
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"To date, all DUBs regulating ferroptosis through the inhibition of system Xc‐/GPX, such as OTU DUB, ubiquitin aldehyde binding 1 (OTUB1), could directly interact with and stabilize SLC7A11 to inhibit ferroptosis, and BRCA1 associated protein 1 can decrease the amount of H2Aub occupying the SLC7A11 promoter to inhibit SLC7A11 expression, thereby inhibiting cystine uptake, resulting in increased levels of lipid peroxidation."
BAP1 increases the amount of H2Aub.
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BAP1 ubiquitinates H2Aub.
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"Additionally, reconstitution of BAP1 into the BAP1-KO cells downregulated H3K27me3 and EZH2 (Fig. 2c), suggesting that BAP1 loss might upregulate H3K27me3 and EZH2 and activate their downstream signaling.A recent study indicated that BAP1 is localized in the endoplasmic reticulum (ER) and bound to the type 3 inositol 1, 4, and 5-triphosphate receptor (IP3R3) [22]."
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"To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells."
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"This could represent a possible connection between BAP1 and expression of HLA in uveal melanoma, as study in mice showed that loss of BAP1 leads to increased levels of EZH2 (and PRC2) with repressed expression of its targets [XREF_BIBR], including thus CIITA, leading ultimately to less HLA class II expression."
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"On the other hand, the occasionally described heterozygous deletions of these genes cannot be completely excluded in our series, because NGS procedure and mode of data analysis were not sensitive to moderate CNV (copy number variation), the detection of which was not the aim of this panel.Germline mutations in BAP1 are known to underlie sometimes melanomas, renal cell carcinomas, malignant mesotheliomas, and some other cancers [31]."
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"This pathway is exploited by immune checkpoint inhibitors in the treatment of melanoma.12 Coordination of the immune response with therapies targeting oncogenes is a possible treatment strategy.12 89CDKN2A, CDK4, MCR1, BAP1, and TERT promoter germline mutations increase melanoma risk within families.15 96 97 No specific germline mutation is associated with acral melanoma yet; in fact, MCR1 variants were less common in acral lentiginous melanoma patients in a Swedish study."
BAP1 affects cell differentiation
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BAP1 inhibits cell differentiation.
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BAP1 bound to ASXL1-MT inhibits cell differentiation. 2 / 2
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BAP1 activates cell differentiation.
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BAP1 inhibits BAP1.
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BAP1 increases the amount of BAP1.
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"DIM promotes proliferation and osteogenic differentiation of MC3T3-E1 cells in vitro, and also plays a bone promoting role by increasing the interaction between BRCA1-Associated Protein 1(BAP1) and Inositol 1,4,5-Trisphosphate Receptor(IP3R), up-regulating the expression of BAP1 and IP3R and downstream storage operation calcium entry (SOCE) related protein Recombinant Stromal Interaction Molecule 1(STIM1)."
reach
"We also detect the mRNA and protein expression level of BAP1, tumors with BAP1 plasmid transfected group exhibited higher BAP1 mRNA and protein expression compared with the control group, suggesting that BAP1 plasmid overexpression could rescue the expression of BAP1 suppressed by miR-31."
BAP1 activates BAP1.
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"While ubiquitination enzyme UBE2O monoubiquitinates the NLS of BAP1 and induces translocation (inactivation) of BAP1 from the nucleus to the cytoplasm, DUB activity of the UCH-domain of BAP1 counteracts the UBE2O activity mediated through the intramolecular interaction between the UCH-domain and COOH-terminal domain of BAP1."
BAP1 decreases the amount of BAP1.
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"Using patient derived lymphoblastoid cell lines, we found that carriers of pathogenic BAP1 germline variants (c. 852_del and c. 1358_1359del) had reduced expression of full-length BAP1, Vimentin and Snail, as compared to controls with wild-type BAP1 (BAP1 WT), whereas BAP1 germline VUS (c. 299T> C and c. 551A> G) or likely benign carriers were not significantly different from wild-type BAP1 WT."
reach
"Furthermore, the BAP1 expression pattern observed in the Human Protein Atlas supports an inverse correlation between BAP1 expression and cell motility, with blood cells, known for their high motility, showing notably lower levels of BAP1 expression (Supplementary Fig. 2 of the SI)."
reach
"Transduction of BAP1 +/- fibroblasts with adenoviruses encoding BAP1, but not the catalytic inactive mutant BAP1 (C91S) XREF_BIBR, XREF_BIBR, rescued IP3R3 protein levels (XREF_FIG), mitochondrial Ca 2+ uptake (XREF_FIG, XREF_FIG, XREF_SUPPLEMENTARY) and resulted in enhanced apoptosis (XREF_FIG)."
reach
"Mechanistically, BAP1 directly binds to IRAK1, competitively inhibits the interaction between IRAK1 and IRAK4, significantly prevents phosphorylation at Thr209 and Thr378 of IRAK1, as well as the autophosphorylation of IRAK1, impeding the dissociation of IRAK1 from the Myddosome complex and the sequential activation NF-κB signaling.Previous studies have demonstrated that IRAK1 undergoes phosphorylation and K63-linked ubiquitination during activation, both of which are essential for the initiation of downstream signaling pathways30, 41."
reach
"However, BAP1 can also form complexes with many other proteins, including the tumor suppressor BRCA1, host cell factor-1 (HCF-1), N-acetylglucosamine transferase, the forkhead box transcription factors FOXK1/2, MBD family proteins MBD5/6, transcription factor YY1 and ubiquitin conjugating enzyme UBE20 [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
reach
"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
reach
"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
sparser
"In addition, a mutation hotspot within the PHD cluster of the KMT2C gene was described, the mutations of which disrupted the interaction of KMT2C with the BAP1 (BRCA1 associated protein-1) tumor suppressor, resulting in poor patient survival in many types of cancer (liver, lung, bladder, and breast)."
reach
"However, BAP1 can also form complexes with many other proteins, including the tumor suppressor BRCA1, host cell factor-1 (HCF-1), N-acetylglucosamine transferase, the forkhead box transcription factors FOXK1/2, MBD family proteins MBD5/6, transcription factor YY1 and ubiquitin conjugating enzyme UBE20 [XREF_BIBR, XREF_BIBR - XREF_BIBR]."
reach
"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
reach
"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
sparser
"In addition, a mutation hotspot within the PHD cluster of the KMT2C gene was described, the mutations of which disrupted the interaction of KMT2C with the BAP1 (BRCA1 associated protein-1) tumor suppressor, resulting in poor patient survival in many types of cancer (liver, lung, bladder, and breast)."
BAP1 affects 2'-O-methyluridine
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BAP1 activates 2'-O-methyluridine.
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BAP1 activates 2'-O-methyluridine. 10 / 11
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"Using BAP1‐competent UM cell lines engineered to reduce BAP1 expression through doxycycline‐induced shRNA expression, we found that reduction of BAP1 correlated with increased histone H2A ubiquitination, suggesting that in UM, BAP1 contributes to epigenetic regulation (Figure 4A)."
Mutated BAP1 activates 2'-O-methyluridine. 4 / 4
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BAP1 inhibits 2'-O-methyluridine.
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BAP1 inhibits 2'-O-methyluridine. 10 / 11
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"It has been found that mutations in BAP1, SF3B1, and EIF1AX in UM with different prognoses exhibit different types of methylation cluster status, and hypermethylation of chromosome 3 in UM is also associated with downregulation of BAP1 gene expression, which was further confirmed in vitro experiments that knockdown of BAP1 gene or deletion of the protein induces effects on methylation status in UM cells, causing UM cells to exhibit a low metastatic risk phenotype [20–22]."
reach
"Interestingly, recent research has revealed that the gain of chromosomal 8q may worsen prognosis by activating macrophage infiltration, and the loss of BAP1 expression may drive T cell infiltration in UM (Gezgin et al., 2017), suggesting that immune infiltration plays a crucial role in the prognosis of UM.Emerging evidence shows that the immune microenvironment is crucial for cancer progression and response to therapeutics (Quail and Joyce, 2013)."
sparser
"For example, analysis of 407 pleural mesothelioma cases and 389 controls with a comprehensive history of asbestos exposure revealed an increased risk of abnormalities in chromosomal region 7p22.2, which includes the gene encoding the Forkhead box protein K1 (FOXK1) that interacts with BAP1 [ xref ]."
| PMC
reach
"Importantly, a correlation was found between BAP1 and INO80 expression in mesothelioma, and re-expression of BAP1 in H226 cells exhibiting low levels of INO80 fully rescued the INO80 levels, showing that the low INO80 expression level in H226 cells was due to a lack of BAP1-mediated INO80 stabilization ."
reach
"More importantly, both wild-type (WT) and C91A mutated BAP1 attenuated the HSF1-SIRT1 interaction (Fig. 5C, Supplementary Fig. S3G), and SIRT1 knockdown resulted in an enhanced binding between HSF1 and BAP1 (Fig. 5D, Supplementary Fig. S3H), indicating that BAP1 and SIRT1 might compete with each other for binding to HSF1."
reach
"However, these interrogations do not undermine our conclusion that BAP1 inhibits HSF1 transcriptional activity independently of its enzymatic activity.As previously stated, the significance of BAP1 in maintenance of genomic integrity, DNA damage repair, cellular metabolism, and cell death is relatively well-established [27–30]."
reach
"These findings imply that the absence of BAP1 can augment cellular sensitivity to specific therapeutic interventions, thereby furnishing a theoretical rationale for therapies aimed at BAP1-associated cancers.Additionally, our prior research has unveiled that BAP1 can modulate the activity of HSF1 through a non-enzymatic mechanism, ultimately impacting the responsiveness to immune checkpoint inhibitors33."
sparser
"For example, analysis of 407 pleural mesothelioma cases and 389 controls with a comprehensive history of asbestos exposure revealed an increased risk of abnormalities in chromosomal region 7p22.2, which includes the gene encoding the Forkhead box protein K1 (FOXK1) that interacts with BAP1 [ xref ]."
| PMC
BAP1 affects DNA repair
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BAP1 activates DNA repair.
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BAP1 activates DNA repair. 10 / 19
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"Indeed, by using a green fluorescent protein (GFP)-based reporter assay employing a recognition site for the rare-cutting I-SceI endonuclease for induction of DSBs , we found that loss of BAP1 caused a substantial reduction of GFP-positive cells, indicating loss of proper DNA repair (Supplementary Fig. 5k)."
reach
"Although LOH of additional genes within Chr 3p21.1 may contribute to tumor suppression, and loss of BAP1 in pancreatic cancer may be secondary—rather than the cause of genomic instability—our mouse model suggests Bap1 ablation suffices to cause defective DNA repair, pancreatitis, and cooperates with oncogenic Kras to promote pancreatic cancer."
BAP1 inhibits DNA repair.
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"We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1. We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers."
reach
"After transfection of Flag-FOXO3a, HA-BAP1 and various ubiquitin mutants (K48, K63, K48R and K63R) into 293T cells, it was observed that BAP1 predominantly reduced the ubiquitin modification of the FOXO3a protein at the K48 position, thereby verified the experimental findings regarding the half-life of FOXO3a."
BAP1 affects Carcinogenesis
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BAP1 activates Carcinogenesis.
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BAP1 activates Carcinogenesis. 10 / 11
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"While RNF2, through H2A monoubiquitination, silences the BCL2 and MCL1 prosurvival genes and thereby induces apoptosis in some cell types, this does not occur in melanocytes, suggesting that BAP1 promotes tumorigenesis in cells that do not engage such RNF2 apoptotic programme.Moving to the p53 tumor suppressor, Karen Vousden (London, UK), who was awarded the CDD Award 2018, retraced the long road leading to her key discoveries of p53 functions."
Mutated BAP1 activates Carcinogenesis. 3 / 3
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BAP1 inhibits Carcinogenesis.
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BAP1 inhibits Carcinogenesis. 9 / 9
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"Therefore, it will be important to investigate the mechanism underlying the tumor-promoting effect of BAP1 inactivation in each cell type.In summary, this study demonstrated that Bap1 loss promotes tumorigenesis only in the tissues in which Bap1 is not engaged in pro-survival gene expression, providing an explanation for the tissue specificity of the BAP1 cancer predisposition syndrome."
reach
"If the loss of either NF2 or BAP1 mediates oncogenesis via the perturbation of Hippo signalling, the failure to take into account the additional Hippo kinase module inactivating events present in PM may have confounded previous efforts to stratify patients according to mutation status."
BAP1 affects Malignant Mesothelioma
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BAP1 activates Malignant Mesothelioma.
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BAP1 activates Malignant Mesothelioma. 7 / 7
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"While homozygous CKO of Bap1, Cdkn2a, or Nf2 alone gave rise to few or no MMs, inactivation of Bap1 cooperated with loss of either Nf2 or Cdkn2a to drive development of MM in ~ 20% of double-CKO mice, and a high incidence (22/26, 85%) of MMs was observed in Bap1; Nf2; Cdkn2a (triple)-CKO mice."
Mutated BAP1 activates Malignant Mesothelioma. 4 / 4
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BAP1 inhibits Malignant Mesothelioma.
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BAP1 binds Malignant Mesothelioma.
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Malignant Mesothelioma binds BAP1. 4 / 4
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sparser
"BAP1 knockdown in MM cell lines has been paradoxically associated to a decreased proliferation, with an accumulation of cells in the S phase of the cell cycle xref , suggesting that BAP1 loss might promote tumorigenesis inducing a delayed, but more permissive, G1/S checkpoint xref ."
BAP1 affects DNA-templated transcription
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BAP1 activates DNA-templated transcription.
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BAP1 activates DNA-templated transcription. 10 / 16
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"p53 binds to the SLC7A11 promoter, directly suppressing its transcription; the nuclear deubiquitinase (DUB) BAP1 represses SLC7A11 transcription by removing histone 2A ubiquitination from the SLC7A11 promoter; and KEAP1 represses SLC7A11 transcription through degrading NRF2, a master transcription factor of antioxidant response and regulator of SLC7A11."
reach
"These included the SETD1A, KMT2C and MLL3, KMT2E and MLL5, and KMT2A and MLL1 methyltransferases that install activating histone H3-lysine 4 trimethylation (H3K4me3) marks; OGT (O-GlcNac transferase), a protein that modulates multiple cell pathways but more recently has been implicated in promoting promoter occupancy of RNAPII; and BAP1 (BRCA1 Associated Protein 1), a deubiquitinase that stimulates transcription, at least in part, by removing repressive histone H2A-K119 monoubiquitin."
reach
"Luchini et al. also reported that BAP1 mutated clear cell renal carcinomas were frequently observed in females and were associated with high tumor grade (p < 0.0001), increased all-cause mortality, cancer-specific mortality, and risk of recurrence.NCOR1P1, Nuclear Receptor Corepressor 1 Pseudogene 1, is predicted to enable transcription corepressor activity, and to be involved in the negative regulation of transcription by RNA polymerase II ."
BAP1 inhibits DNA-templated transcription.
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"We report a critical link between BAP1 complex and BRD4, which is bridged by the physical interaction between ASXL3 and BRD4 in an SCLC subtype (SCLC-A), which expresses a high level of ASCL1. We further showed that ASXL3 functions as an adaptor protein, which directly interacts with BRD4's extra-terminal (ET) domain via a novel BRD4 binding motif (BBM), and maintains chromatin occupancy of BRD4 to active enhancers."
sparser
"Across clear cell- and papillary-associated RCC subtypes in TCGA cohort, worse survival was associated with SETD2 or BAP1 mutation, with their related gene transcriptional signatures involving greater numbers of RCC cases and also being predictive of worse outcome ( xref , xref )."
sparser
"In pleural and peritoneal mesothelioma, co-occurring alterations occurred on the same chromosome or in close proximity for PBRM1–BAP1 (both 3p21) and SETD2–BAP1 (both 3p21), which was observed in the TCGA cohort but not in the recent publication by Zauderer and colleagues [ xref ]."
sparser
"Here, we focus on the impact of individual mutations of PBRM1 , BAP1 , and SETD2 on cancer specific survival in an expanded version of our original cohort (3 additional patients and several more months of followup and events) and further demonstrate the association of BAP1 and SETD2 mutations with worse cancer specific survival (the TCGA cohort n=421), providing a molecular link between gene mutations and cancer specific outcomes in ccRCC."
sparser
"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
sparser
"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate ( xref ), and 2) the nuclei of BAP1 WT cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 +/− cells ( xref )."
sparser
"CoIP experiments in cells co-transfected with full-length Myc-tagged BAP1 (Myc- BAP1 ) and HA-tagged full-length HIF-1α, or HIF-1α fragments covering residues 74 to 826 [HIF-1α(74-826)], 2-400 [HIF-1α(2-400)], 401-826 [HIF-1α(401-826)] ( xref ), confirmed that BAP1 binds to the N terminus region of HIF-1α [HIF-1α(2-400)] ( xref )."
sparser
"Across clear cell- and papillary-associated RCC subtypes in TCGA cohort, worse survival was associated with SETD2 or BAP1 mutation, with their related gene transcriptional signatures involving greater numbers of RCC cases and also being predictive of worse outcome ( xref , xref )."
sparser
"In pleural and peritoneal mesothelioma, co-occurring alterations occurred on the same chromosome or in close proximity for PBRM1–BAP1 (both 3p21) and SETD2–BAP1 (both 3p21), which was observed in the TCGA cohort but not in the recent publication by Zauderer and colleagues [ xref ]."
sparser
"Here, we focus on the impact of individual mutations of PBRM1 , BAP1 , and SETD2 on cancer specific survival in an expanded version of our original cohort (3 additional patients and several more months of followup and events) and further demonstrate the association of BAP1 and SETD2 mutations with worse cancer specific survival (the TCGA cohort n=421), providing a molecular link between gene mutations and cancer specific outcomes in ccRCC."
sparser
"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
sparser
"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate ( xref ), and 2) the nuclei of BAP1 WT cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 +/− cells ( xref )."
sparser
"CoIP experiments in cells co-transfected with full-length Myc-tagged BAP1 (Myc- BAP1 ) and HA-tagged full-length HIF-1α, or HIF-1α fragments covering residues 74 to 826 [HIF-1α(74-826)], 2-400 [HIF-1α(2-400)], 401-826 [HIF-1α(401-826)] ( xref ), confirmed that BAP1 binds to the N terminus region of HIF-1α [HIF-1α(2-400)] ( xref )."
sparser
"The faithful Vhl-Bap1 and Vhl-Pbrm1 GEM models developed by Gu and colleagues add to the recent salvo of GEM models of ccRCC based upon concurrent deletion of Vhl, p53 , and Rb1 by Frew and colleagues or the inactivation of Vhl and Cdkn2a with concurrent activation of MYC by our group ( xref , xref )."
sparser
"Using computer molecular modeling of UCHL5 structures, we predicted that the BAP1-ULD domain folds back to the BAP1-UCH catalytic domain and that the ASXL2-AB box stabilizes the UCH catalytic loop via a unique BAP1 mechanism not seen in other UCH proteins, allowing for ubiquitin to fit into the active site ( xref , xref )."
sparser
"The faithful Vhl-Bap1 and Vhl-Pbrm1 GEM models developed by Gu and colleagues add to the recent salvo of GEM models of ccRCC based upon concurrent deletion of Vhl, p53 , and Rb1 by Frew and colleagues or the inactivation of Vhl and Cdkn2a with concurrent activation of MYC by our group ( xref , xref )."
sparser
"Using computer molecular modeling of UCHL5 structures, we predicted that the BAP1-ULD domain folds back to the BAP1-UCH catalytic domain and that the ASXL2-AB box stabilizes the UCH catalytic loop via a unique BAP1 mechanism not seen in other UCH proteins, allowing for ubiquitin to fit into the active site ( xref , xref )."
sparser
"Transcriptomic and mechanistic analyses revealed that disruption of the BAP1-SUFU axis alters cell-cycle transcriptional programs through a Hh-independent mechanism and implicates E2F1 as a downstream regulator, which was confirmed by Western blot and rescue experiments demonstrating its essential role in driving the proliferative phenotype."
PT33 affects BAP1
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sparser
"Therefore, we carried out co-IP/WB assays with ectopic expression of Myc- HERC2 (3559–4834 aa 18 ), and found that after IR, PT33-bound BAP1 showed markedly stronger interaction with BRCA1 than uncombined BAP1; only PT33-bound BAP1 could recruit HERC2 to target BRCA1, but not uncombined BAP1."
BAP1 affects cell cycle
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BAP1 activates cell cycle.
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BAP1 inhibits cell cycle.
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BAP1 inhibits cell cycle. 8 / 8
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"Interestingly, there was no substantial difference in cell viability, BrdU incorporation or cell cycle profile between BAP1 deficient and control cells after stable expression of the shRNA constructs for at least 14days, indicating that the initial cell cycle inhibition caused by BAP1 depletion was transient."
reach
"These results indicated that BAP1 suppressed ICC cell proliferation, cell cycle progression, and invasion via inhibiting ERK1/2 and JNK/c-Jun signaling pathways.To further validate these findings, we used inhibitors of the ERK1/2 pathway (U0126) and JNK/c-Jun pathway (SP600125) in RBE-shBAP1 cells."
sparser
"Transcriptomic and mechanistic analyses revealed that disruption of the BAP1-SUFU axis alters cell-cycle transcriptional programs through a Hh-independent mechanism and implicates E2F1 as a downstream regulator, which was confirmed by Western blot and rescue experiments demonstrating its essential role in driving the proliferative phenotype."
BAP1 affects PT33
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sparser
"Therefore, we carried out co-IP/WB assays with ectopic expression of Myc- HERC2 (3559–4834 aa 18 ), and found that after IR, PT33-bound BAP1 showed markedly stronger interaction with BRCA1 than uncombined BAP1; only PT33-bound BAP1 could recruit HERC2 to target BRCA1, but not uncombined BAP1."
reach
"Therefore, given the better effect of BAP1 in elevating MYCN protein levels in our experimental settings, the BAP1 will be our major focus in the remainder of the study.Next, we performed the protein half-life assay and ubiquitination assay to further confirm whether BAP1 is a bona fide DUB for MYCN to plays a vital role in positively regulating MYCN protein abundance."
BAP1 affects Cell Survival
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BAP1 inhibits Cell Survival.
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BAP1 inhibits Cell Survival. 8 / 9
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"Furthermore, our results reveled that BaP1 reduced cell survival and cell motility, two desirable properties for an anticancer drug.Interestingly, when we treated RKO cells with higher doses of BaP1, 2 × IC and 4 × IC , concentrations that still have a reduced inhibitory effect in the noncancerous colon cell line NCM460, we observed well-established and correlated phenotypes."
BAP1 activates Cell Survival.
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BAP1 affects ASXL1-MT
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BAP1 binds ASXL1-MT.
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"To examine the cooperation between ASXL1-MT and BAP1 in human RUNX1-ETO cells, we transduced ASXL1-MT or ASXL1-MT-K351R (coexpressing GFP) together with BAP1 or BAP1-C91S (coexpressing NGFR), and monitored changes of the frequency of the GFP + NGFR + double positive fraction in culture."
reach
"In addition to these reports implicating BAP1 in myeloid transformation, the present results identify the underlying molecular mechanisms by which ASXL1-MT and BAP1 complex induce myeloid transformation; BAP1 plays a necessary role in maintaining aberrant posterior HOXA expression in ASXL1-mutant leukemia and in sustaining their leukemic proliferation."
BAP1 ubiquitinates ASXL1-MT.
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sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
reach
"More importantly, both wild-type (WT) and C91A mutated BAP1 attenuated the HSF1-SIRT1 interaction (Fig. 5C, Supplementary Fig. S3G), and SIRT1 knockdown resulted in an enhanced binding between HSF1 and BAP1 (Fig. 5D, Supplementary Fig. S3H), indicating that BAP1 and SIRT1 might compete with each other for binding to HSF1."
BAP1 affects homologous recombination
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BAP1 activates homologous recombination.
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BAP1 activates homologous recombination. 9 / 9
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BAP1 activates homologous recombination. 3 / 3
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"We reasoned that if BAP1 interacts with BARD1 to modulate homologous recombination and possibly other cellular pathways, germline BARD1 mutations might also predispose to mesothelioma, and that these patients might have a better prognosis, similar to carriers of germline BAP1 mutations."
BAP1 inhibits homologous recombination.
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BAP1 affects calcium(2+)
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BAP1 increases the amount of calcium(2+).
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BAP1 activates calcium(2+).
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sparser
"On analyses adjusted only for cohort, we found that mutations in BAP1 ( n = 1049 for analysis; hazard ratio [HR]: 2.10; 95% confidence interval [CI]: 1.44–3.04; q < 0.001) and TP53 ( n = 784 for analysis; HR: 2.63; 95% CI: 1.36–5.08; q = 0.028) were significantly associated with increased risk of death from cancer after adjustment for multiple comparisons using competing risks regression ( xref )."
reach
"However, restoring BAP1 in p53 deficient cells still inhibited SLC7A11 expression (XREF_SUPPLEMENTARY - XREF_SUPPLEMENTARY), and the fold change in SLC7A11 expression by BAP1 restoration in p53 deficient cells was similar to that in p53-proficient cells (XREF_SUPPLEMENTARY), suggesting that BAP1 represses SLC7A11 expression independent of p53."
sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
ASXL1-MT affects BAP1
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ASXL1-MT binds BAP1.
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"To examine the cooperation between ASXL1-MT and BAP1 in human RUNX1-ETO cells, we transduced ASXL1-MT or ASXL1-MT-K351R (coexpressing GFP) together with BAP1 or BAP1-C91S (coexpressing NGFR), and monitored changes of the frequency of the GFP + NGFR + double positive fraction in culture."
reach
"In addition to these reports implicating BAP1 in myeloid transformation, the present results identify the underlying molecular mechanisms by which ASXL1-MT and BAP1 complex induce myeloid transformation; BAP1 plays a necessary role in maintaining aberrant posterior HOXA expression in ASXL1-mutant leukemia and in sustaining their leukemic proliferation."
ASXL1-MT activates BAP1.
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"The nuclear localized deubiquitylating enzyme BAP1 XREF_BIBR, XREF_BIBR, which is responsible for histone modification in transcription regulation XREF_BIBR, XREF_BIBR, can be phosphorylated by Ataxia telangiectasia mutated (ATM) and participates in DNA double-strand break (DSB) repair through regulating histone 2A and H2AX ubiquitylation XREF_BIBR, XREF_BIBR."
sparser
"Numerous studies have demonstrated that truncated ASXL1 mutants, including the ASXL1 fragment containing amino acids 1–587, promote myeloid transformation by forming a stable polycomb-repressive deubiquitinase (PR-DUB) complex with BAP1, enhancing BAP1 deubiquitinase (DUB) activity [ xref , xref , xref ]."
sparser
"The interaction with BRCA1 and BARD1 form a tumor suppressor heterodimeric complex. [ xref ] BAP1 regulates cell proliferation and interacts with histone-modifying complexes during cell division. [ xref , xref ] BAP1 also forms the Polycomb group repressive deubiquitinase complex (PR-DUB) through interaction with ASXL1, which is involved several developmental processes. [ xref ] Because of this functional complexity, BAP1 germline mutations predispose individuals to the aggressive tumor phenotypes."
reach
"p53 binds to the SLC7A11 promoter, directly suppressing its transcription; the nuclear deubiquitinase (DUB) BAP1 represses SLC7A11 transcription by removing histone 2A ubiquitination from the SLC7A11 promoter; and KEAP1 represses SLC7A11 transcription through degrading NRF2, a master transcription factor of antioxidant response and regulator of SLC7A11."
sparser
"Numerous studies have demonstrated that truncated ASXL1 mutants, including the ASXL1 fragment containing amino acids 1–587, promote myeloid transformation by forming a stable polycomb-repressive deubiquitinase (PR-DUB) complex with BAP1, enhancing BAP1 deubiquitinase (DUB) activity [ xref , xref , xref ]."
sparser
"The interaction with BRCA1 and BARD1 form a tumor suppressor heterodimeric complex. [ xref ] BAP1 regulates cell proliferation and interacts with histone-modifying complexes during cell division. [ xref , xref ] BAP1 also forms the Polycomb group repressive deubiquitinase complex (PR-DUB) through interaction with ASXL1, which is involved several developmental processes. [ xref ] Because of this functional complexity, BAP1 germline mutations predispose individuals to the aggressive tumor phenotypes."
BAP1 affects DNA Damage
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BAP1 activates DNA Damage. 10 / 10
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Mutated BAP1 activates DNA Damage. 3 / 3
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3
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"However, the spontaneous development of mesotheliomas in Bap1 +/- mice not exposed to asbestos, and the development of multiple cancer types in carriers of BAP1 mutations (XREF_FIG), including tumor types that have not been associated with known carcinogens, suggests that BAP1 mutations also drive tumor growth independently of genotoxic stress, perhaps by favoring the accumulation of age related DNA damage."
sparser
"We combine genetics, microscopy, simulations, and biochemical analyses to show that V. cholerae cells are not attracted to the main matrix component ( Vibrio polysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1."
sparser
"Crucially, the recognition of community membership is closely tied to the active secretion of VPS: cells coated by VPS – which only occurs when the exopolysaccharide is actively being produced – are recognized by the existing VPS-Bap1 network or other VPS-coated cells and consequently included within the biofilm through bridging-aggregation."
sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
sparser
"Real-time RT-PCR analysis demonstrates that lentiviral transduction of FLAG-BAP1 significantly decreased the mRNA level of NRF2 target genes such as heme oxygenase-1 (Hmox1), NADPH:quinone oxidoreductase-1 (Nqo1), glutamate cysteine ligase catalytic subunit (Gclc), and aldo-keto reductase family 1 member B10 (Akr1b10) in A549 cells ( xref D)."
BAP1 affects cell migration
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1
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BAP1 activates cell migration.
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7
BAP1 activates cell migration. 7 / 7
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7
reach
"BAP1 promotes breast cancer cell proliferation and metastasis through deubiquitination of KLF5.33 High BBS1 gene expression facilitates survival of malignant pleural mesothelioma.34 Crosstalk between macrophages and cancer cells via CCR2 and CX3CR1 is the underlying mechanism driving lung cancer.35 RIPK4 overexpression promotes pancreatic cancer cell migration and invasion through PEBP1 degradation-induced activation of the RAF1/MEK/ERK pathway."
BAP1 inhibits cell migration.
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1
4
sparser
"We combine genetics, microscopy, simulations, and biochemical analyses to show that V. cholerae cells are not attracted to the main matrix component ( Vibrio polysaccharide, VPS), but can be attached to each other and to the VPS network through surface-associated VPS and crosslinks formed by the protein Bap1."
sparser
"Crucially, the recognition of community membership is closely tied to the active secretion of VPS: cells coated by VPS – which only occurs when the exopolysaccharide is actively being produced – are recognized by the existing VPS-Bap1 network or other VPS-coated cells and consequently included within the biofilm through bridging-aggregation."
sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
BAP1 affects Histone_H2A
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12
BAP1 ubiquitinates Histone_H2A.
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7
BAP1 ubiquitinates Histone_H2A. 7 / 7
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7
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"BRCA1-associated protein 1 (BAP1) [18], the crucial constituent of the deubiquitinase complex, attenuated the initiation and extension of SLC7A11 transcription by deubiquitinating histone 2A, while the steady-state levels and half-life of SLC7A11 were improved by combination with the ovarian tumor family member deubiquitinase (OTUB1) [19]."
BAP1 deubiquitinates Histone_H2A.
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5
BAP1 deubiquitinates Histone_H2A. 5 / 5
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5
reach
"BRCA1-associated protein 1 (BAP1) [18], the crucial constituent of the deubiquitinase complex, attenuated the initiation and extension of SLC7A11 transcription by deubiquitinating histone 2A, while the steady-state levels and half-life of SLC7A11 were improved by combination with the ovarian tumor family member deubiquitinase (OTUB1) [19]."
reach
"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate (Fig. 2A), and 2) the nuclei of BAP1 cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 cells (Fig. 2 B and C)."
reach
"Aligning the crystal structure of HIF-1α-HIF-1β complex (PDB ID: 4zpr) (49) to our structural model for the binding complex of BAP1-HIF-1α showed that both BAP1 and HIF-1β bind to the same residues of HIF-1α (1-73) on the DNA; however, in Fig. 3B, we demonstrate that BAP1, HIF-1α and the DNA form a complex without HIF-1β."
reach
"Therefore, our data indicate that BAP1 is not required for HIF-1α-HIF-1β complex formation to functionally bind to DNA, that HIF-1β is not required for BAP1-HIF-1α complex formation to functional binding to DNA, and that although DNA facilitates the binding of BAP1 and HIF-1α, it is not required to maintain the binding of both BAP1-HIF-1α and BAP1-HIF-1β."
BAP1 affects Genomic Instability
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12
BAP1 inhibits Genomic Instability.
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6
BAP1 activates Genomic Instability.
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6
BAP1 activates Genomic Instability. 6 / 6
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6
reach
"The complement factor H-related (CFHR) protein family induces the ubiquitination of polo-like kinase 1 (PLK1) at lysine 209 (Zhu et al., 2021a), BRCA1-associated protein 1 (BAP1) enhances genomic stability (Perkail et al., 2020), and USP9X is found to restrain tumor growth in the patient-derived tumor xenograft (PDX) model (Pal et al., 2018)."
sparser
"Real-time RT-PCR analysis demonstrates that lentiviral transduction of FLAG-BAP1 significantly decreased the mRNA level of NRF2 target genes such as heme oxygenase-1 (Hmox1), NADPH:quinone oxidoreductase-1 (Nqo1), glutamate cysteine ligase catalytic subunit (Gclc), and aldo-keto reductase family 1 member B10 (Akr1b10) in A549 cells ( xref D)."
BAP1 affects E3_Ub_ligase
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6
6
BAP1 inhibits E3_Ub_ligase.
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6
1
BAP1 binds E3_Ub_ligase.
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E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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sparser
"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
E3_Ub_ligase binds BAP1. 2 / 2
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MiR-31 affects BAP1
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MiR-31 decreases the amount of BAP1.
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6
MiR-31 inhibits BAP1.
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3
reach
"Finally, the cells transfected with miR-31 and the BAP1 overexpression plasmid exhibited significantly lower proliferation rates compared with the cells transfected with miR-31 and the control plasmid, suggesting that miR-31-resistant BAP1 could rescue the suppression of BAP1 by miR-31 and attenuate the proliferative effect of miR-31."
MiR-31 binds BAP1.
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2
sparser
"On analyses adjusted only for cohort, we found that mutations in BAP1 ( n = 1049 for analysis; hazard ratio [HR]: 2.10; 95% confidence interval [CI]: 1.44–3.04; q < 0.001) and TP53 ( n = 784 for analysis; HR: 2.63; 95% CI: 1.36–5.08; q = 0.028) were significantly associated with increased risk of death from cancer after adjustment for multiple comparisons using competing risks regression ( xref )."
MP46 affects BAP1
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11
sparser
"We further investigated the metabolite levels related to FA metabolism and observed MP46 had significantly lower levels of FAs and palmitoylcarnitine, which is involved in FA transport into mitochondria for oxidation compared to MP46-BAP1, but higher acetyl-carnitine levels, a byproduct of FAO ( xref )."
BAP1 affects metabolic process
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11
BAP1 inhibits metabolic process.
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7
BAP1 inhibits metabolic process. 7 / 7
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"Moreover, BAP1 deficiency drives the reprogramming of cell metabolism, promoting anaerobic glycolysis for energy production rather than mitochondrial respiration and increasing extracellular lactate secretion which induces immune evasion, tumour growth and cell malignant transformation.BAP1 emerges as a highly tissue-specific and context-specific tumour suppressor participating to the biology of the tumour with multiple mechanisms and different levels (summary in Table 1)."
reach
"Gene ontology (GO) analysis of 354 BAP1 upregulated and 187 BAP1 downregulated genes revealed that, while BAP1 upregulated genes were enriched in diverse cellular processes (XREF_SUPPLEMENTARY and XREF_SUPPLEMENTARY), the genes that were downregulated by BAP1 showed striking enrichment in metabolism related biological processes, among which " response to oxidative stress " was the most significantly enriched (XREF_FIG and XREF_SUPPLEMENTARY)."
BAP1 activates metabolic process.
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4
BAP1 affects glycolytic process
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BAP1 activates glycolytic process.
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7
BAP1 inhibits glycolytic process.
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4
BAP1 inhibits glycolytic process. 4 / 4
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4
reach
"XREF_FIG shows that BAP1 +/- fibroblasts transduced with AdBAP1 had reduced glycolysis and glycolytic capacity; in contrast, AdC91S was ineffective at reducing glycolysis (rate of glycolysis in BAP1 +/- transduced with : AdGFP 24.94 +/-1.77 mpH and min, AdBAP1 6.92 +/-0.24 mpH and min, AdBAP1 (C91S) 20.33 +/-2.92 mpH and min; glycolytic capacity : AdGFP 30.33 +/-1.71 mpH and min, AdBAP1 11.50 +/-0.43 mpH and min, AdC91S 25.08 +/-3.25 mpH and min)."
reach
"The oxygen-dependent mechanisms that cause HIF-1α degradation and the genes that suppress HIF-1α in hypoxia have been studied in detail (10, 34), while the gene products that by facilitating HIF-1α expression and activity in hypoxia influence tumor invasion and metastases, remain largely unknown.We reported that reduced BAP1 levels increase aerobic glycolysis (5)."
BAP1 affects cell adhesion
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BAP1 activates cell adhesion. 10 / 11
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11
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"The loss of function in the defective mutants is unlikely due to changes in the production or secretion level of the mutant protein (Supplementary Fig. 4a–d), and in all defective strains the adhesion defects can be rescued by WT Bap1/RbmC expressed from a plasmid (Supplementary Fig. 4e)."
BAP1 affects MP46
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11
sparser
"We further investigated the metabolite levels related to FA metabolism and observed MP46 had significantly lower levels of FAs and palmitoylcarnitine, which is involved in FA transport into mitochondria for oxidation compared to MP46-BAP1, but higher acetyl-carnitine levels, a byproduct of FAO ( xref )."
TG2-179-1 affects BAP1
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10
TG2-179-1 inhibits BAP1.
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7
TG2-179-1 binds BAP1.
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3
reach
"Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) experiments revealed that 1) HIF-1α and BAP1 bind to each other and co-precipitate (Fig. 2A), and 2) the nuclei of BAP1 cells contained significantly more PLA positive signals—evidence of BAP1 and HIF-1α interaction—than BAP1 cells (Fig. 2 B and C)."
reach
"Aligning the crystal structure of HIF-1α-HIF-1β complex (PDB ID: 4zpr) (49) to our structural model for the binding complex of BAP1-HIF-1α showed that both BAP1 and HIF-1β bind to the same residues of HIF-1α (1-73) on the DNA; however, in Fig. 3B, we demonstrate that BAP1, HIF-1α and the DNA form a complex without HIF-1β."
reach
"Therefore, our data indicate that BAP1 is not required for HIF-1α-HIF-1β complex formation to functionally bind to DNA, that HIF-1β is not required for BAP1-HIF-1α complex formation to functional binding to DNA, and that although DNA facilitates the binding of BAP1 and HIF-1α, it is not required to maintain the binding of both BAP1-HIF-1α and BAP1-HIF-1β."
BAP1 affects immune response
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10
BAP1 inhibits immune response.
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6
BAP1 activates immune response.
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4
BAP1 activates immune response. 4 / 4
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4
reach
"Here, our molecular profiling data revealed that BAP1-deficient MPM is enriched for immune-related pathways (e.g., IFN-α/γ response) and strongly correlates with the gene signature of DCs, a professional antigen-presenting cell type that induces the activation and differentiation of naive T lymphocytes,35 suggesting that BAP1 contributes to antitumor immunity in MPM beyond its function intrinsic to cancer cells.First, we observed that BAP1-deficient MPM exhibited increased expression of several inhibitory immune checkpoints, such as PD-L1, PD-1, and LAG3."
BAP1 affects PRC2_complex
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4
BAP1 inhibits PRC2_complex.
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BAP1 binds PRC2_complex.
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BAP1 binds PRC2_complex. 4 / 4
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sparser
"ASXL1 functions in transcriptional repression through its interaction with PRC2 and BAP1. xref BCORL1 is a transcriptional co-repressor that interacts with PCGF1, a core complex of the PRC1.1 complex. xref The RUNX1-CBF-b heterodimer mediates transcription by binding to RUNX sites, but also represses transcription by interacting and recruiting BMI1 of the PRC1 complex to target sites. xref IKZF1 regulates transcription by interacting with repressive epigenetic complexes such as HDAC1, HDAC2, CHD3, CHD4, and SWI/SNF complex, and also recruits PRC2 to target gene loci in T cells. xref Thus, while the commonly mutated genes in CML have their own exclusive roles in transcriptional regulation, they also share a striking commonality as modulators of the PRC."
BAP1 affects H2AK119Ub
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10
BAP1 affects gene expression
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9
BAP1 activates gene expression. 9 / 9
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9
reach
"In this study, we identified a key signaling pathway involving the histone H2AK119 deubiquitinase BRCA1 associated protein 1 (BAP1), the interferon regulatory factor interferon regulatory factor 1 (IRF1), and the MHC-II transactivator class II transactivator (CIITA), which directly activates MHC-II gene expression."
reach
"Based on our independent analysis, BAP1 deficiency in myeloid progenitors led to a dramatic increase of H3K27me3 levels at the MHC-II loci (Supplemental Figure 2G), and a substantial reduction in MHC-II gene expression (Supplemental Figure 2, H and I), which is consistent with our conclusions."
BAP1 affects double-strand break repair
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9
BAP1 activates double-strand break repair.
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5
BAP1 inhibits double-strand break repair.
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4
BAP1 affects angiogenesis
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8
BAP1 inhibits angiogenesis. 9 / 9
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1
8
reach
"Furthermore, we observed that BaP1 decreased angiogenesis, characterized by a significant decrease in the vascularization formed around the tumors, as well as reduced tumor proliferation evidenced by the reduced levels of Ki67 expression in the tumors treated with the compound.Overall, our data highlights BaP1 as a molecule with a potent and selective anticancer activity against CRC cells and as a very interesting agent to disturb and counteract the important roles of lysosome in cancer."
reach
"In view of previous reports that IL-1β induces PGE production via up-regulation of COX-2 and PGESm-1 expression in several cell types, including synovial fibroblasts , it is plausible to suggest that, under the present experimental conditions, IL-1β up-regulates BaP1-stimulated production of PGE by inducing expression of COX-2 and/or mPGES-1 in FLSs."
reach
"Partially consistent with our results, BAP1 was unfolded to increase the COX-2 and mPGES-1 expression by activating the NF-κB signaling pathway and inducing the release of IL-1β (Viana et al. 2020), but this study failed to explore the regulatory role of BAP1 mutations on the NF-κB signaling pathway."
3p21.1 losses affects BAP1
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9
sparser
"We could also confirm that the short fragment of BAP1-ULD domain and 14-3-3-alpha helices 7-9 regions facilitate interaction between these two proteins (Fig. xref ), while the interaction between BAP1 and 14-3-3-σ inactive mutants were reduced compared to the full-length 14-3-3-σ (Fig. xref )."
reach
"However, a limitation of our study is that eye pigmentation is deduced from genotypes, which are also risk SNPs for UM, making it challenging to derive causal statements.Status of chromosome 3 and BAP1 delineates 2 UM subtypes, M3 and BAP1-inactivated high-risk tumors and D3 and wild-type BAP1 low-risk tumors (2-4,8)."
reach
"Besides, several other transcription factors or tumor suppressors, such as activating transcription factor 3 (ATF3), BRCA1 associated protein-1 (BAP1), ADP-ribosylation factor (ARF), and Kelch-like ECH-associated protein 1 (KEAP1), diminish the expression or suppress the activity of SLC7A11 to induce ferroptosis in cancer cells (Fan et al. 2017; Roh et al. 2017; Wang et al. 2020; Zhang et al. 2018b)."
MLL2 affects BAP1
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8
sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
reach
"S4G), indicating an SL interaction between BAP1 and KDM5C in UMRC6 cells.To determine whether the abovementioned SL interactions exist in patients with cancer, we checked The Cancer Genome Atlas (TCGA) data for somatic mutations targeting TSC2/LKB1 in non–small cell lung cancer and BAP1/KDM5C in ccRCC."
reach
"In all BAP1 IP samples, but not the negative control normal IgG samples endogenous COPA coimmunoprecipitates with endogenous BAP1.We note that only a small fraction of total COPA binds to BAP1 as input levels are much higher than COPA levels in the coIP, correlating with the stoichiometry observed in the AP-MS experiment (Fig 5A and S2 File)."
| PMC
reach
"To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1-associated protein 1 (BAP1), methylthioadenosine (MTAP), 5-hydroxymethylcitosine (5-hmC), glucose transporter 1 (GLUT1), insulin like-growth factor II messenger RNA-binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin-dependent kinase inhibitor 2A (CDKN2A) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells."
sparser
"We could also confirm that the short fragment of BAP1-ULD domain and 14-3-3-alpha helices 7-9 regions facilitate interaction between these two proteins (Fig. xref ), while the interaction between BAP1 and 14-3-3-σ inactive mutants were reduced compared to the full-length 14-3-3-σ (Fig. xref )."
BAP1 affects miR-31
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8
BAP1 inhibits miR-31.
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3
reach
"Finally, the cells transfected with miR-31 and the BAP1 overexpression plasmid exhibited significantly lower proliferation rates compared with the cells transfected with miR-31 and the control plasmid, suggesting that miR-31-resistant BAP1 could rescue the suppression of BAP1 by miR-31 and attenuate the proliferative effect of miR-31."
BAP1 activates miR-31.
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3
BAP1 binds miR-31.
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2
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8
BAP1 inhibits epithelial to mesenchymal transition.
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6
BAP1 activates epithelial to mesenchymal transition.
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2
reach
"A study reported that BAP1 interacts directly with and localizes to γ-tubulin during mitosis and that BAP1 stabilizes γ-tubulin via deubiquitination to support microtubule nucleation and mitotic spindle assembly, thereby ensuring chromosome segregation and preventing chromosome abnormalities."
reach
"In conclusion, the results from the present study provide evidence to suggest that BAP1 and possibly PARP-3 repress hTERT transcription within breast cancer cells, which supports the hypothesis that multiple sequences on human chromosome 3p may be responsible for regulating hTERT transcription."
reach
"Partially consistent with our results, BAP1 was unfolded to increase the COX-2 and mPGES-1 expression by activating the NF-κB signaling pathway and inducing the release of IL-1β (Viana et al. 2020), but this study failed to explore the regulatory role of BAP1 mutations on the NF-κB signaling pathway."
reach
"However, it remains unknown how BAP1 mutations may mechanistically lead to immune suppression.As a potential explanation, we found here that BAP1 loss results in upregulation of PROS1 in UM cells through epigenetic mechanisms involving H3K27ac accumulation at the PROS1 locus, consistent with our previous findings [18]."
reach
"For example, differentiation to mature neurons and glia could require antagonism of PRC-mediated transcriptional repression.We were thus intrigued by our serendipitous discovery that Bap1 deletion in ENS lineages caused profound bowel dysfunction and early death in mice, mimicking human nCIPO or HSCR physiology."
BAP1 affects MLL2
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8
sparser
"To determine whether MBD5 and MBD6 can also bind to chromatin similar to other BAP1 subunits, we conducted Chromatin Immunopreciptiation Sequencing (ChIP-seq) and determined the chromatin binding profiles of MBD5 and MBD6 with our validated homemade antibodies (Additional file xref : Fig. S1F)."
reach
"S4G), indicating an SL interaction between BAP1 and KDM5C in UMRC6 cells.To determine whether the abovementioned SL interactions exist in patients with cancer, we checked The Cancer Genome Atlas (TCGA) data for somatic mutations targeting TSC2/LKB1 in non–small cell lung cancer and BAP1/KDM5C in ccRCC."
BAP1 affects H2AK119ub
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8
BAP1 activates H2AK119ub.
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6
reach
"Such as, the mutant ASXL1 (ASXL1-MT)/BAP1 complex can impair the multidirectional differentiation of HSPCs (except to monocytes) and promote RUNX1-ETO-induced murine c-Kit+ progenitor cell leukemogenesis by removing H2AK119ub, which drives the upregulation of the HOXA gene and interferon regulatory factor 8 (IRF8) [135]."
BAP1 inhibits H2AK119ub.
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2
reach
"In all BAP1 IP samples, but not the negative control normal IgG samples endogenous COPA coimmunoprecipitates with endogenous BAP1.We note that only a small fraction of total COPA binds to BAP1 as input levels are much higher than COPA levels in the coIP, correlating with the stoichiometry observed in the AP-MS experiment (Fig 5A and S2 File)."
| PMC
BAP1 affects ASXL
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8
reach
"Although H2Aub was previously involved in cell proliferation , it is not clear, at this time, whether the observed effects of ASXL2/BAP1 defective in monoubiquitination are solely due to disruption of H2A deubiquitination or the effect of BAP1/ASXL complexes on other substrates.Our data suggest that the signaling pathway we characterized here is important for tumor suppression."
reach
"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
reach
"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
sparser
"Having established the multi-mUb of BAP1 699–729 by UBE2O, we asked whether TNPO1 binding to BAP1 699–729 would down-regulate the ubiquitin ligase activity of UBE2O. Preincubation of the FITC-labeled BAP1 699–729 with one or two molar ratios of TNPO1 for 1 h before initiating the mUb by UBE2O resulted in a substantially reduced level of multi-mUb of BAP1 699–729 in a TNPO1 dose–dependent manner ( xref ; and xref )."
sparser
"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
RING finger domain affects BAP1
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7
sparser
"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
sparser
"Recombinant importin-αs and TNPO1 were expressed in Escherichia coli and purified to homogeneity to investigate their interactions with the CTD of BAP1 (residues 596–729) fused with a maltose-binding protein (MBP) tag (hereafter MBP-BAP1 CTD ) by size-exclusion chromatography (SEC; xref )."
sparser
"In gastric cancer, DIM exerts antitumor effects through multiple mechanisms: Induction of ferroptosis via the BAP1-IP3R axis [ xref ]; STIM1-mediated store-operated calcium entry leading to cell death [ xref ]; inhibition of proliferation and induction of apoptosis via the TRAF2-p38 signaling pathway [ xref ]; potentiation of paclitaxel’s antitumor effects through the Akt/FOXM1 signaling cascade [ xref ]; suppression of cell growth via Hippo signaling pathway activation [ xref ]; activation of the aryl hydrocarbon receptor pathway, promoting its nuclear translocation, inducing apoptosis, delaying cell cycle progression, and inhibiting proliferation [ xref ]."
reach
"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
reach
"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
reach
"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15
BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."
BAP1 affects localization
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1
6
BAP1 activates localization.
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4
BAP1 inhibits localization.
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2
sparser
"Having established the multi-mUb of BAP1 699–729 by UBE2O, we asked whether TNPO1 binding to BAP1 699–729 would down-regulate the ubiquitin ligase activity of UBE2O. Preincubation of the FITC-labeled BAP1 699–729 with one or two molar ratios of TNPO1 for 1 h before initiating the mUb by UBE2O resulted in a substantially reduced level of multi-mUb of BAP1 699–729 in a TNPO1 dose–dependent manner ( xref ; and xref )."
reach
"Taken together, we concluded that Bap1 directly binds SMN and prevents SMN degradation by posttranslational deubiquitination of SMN.Since a lysine residue is one of the predominant targets for ubiquitination, we examined which of the lysine residues in SMN is critical for its ubiquitin-dependent degradation by introducing a non-lysine mutation on phylogenetically conserved lysine residues (Supplemental Figure 8A)."
reach
"These results indicate that Bap1 posttranscriptionally regulates SMN levels and thus affects the function of SMN in FAPs.To test the direct interaction between Bap1 and SMN, we performed endogenous reciprocal immunoprecipitation experiments using freshly isolated FAPs and revealed that Bap1 directly binds SMN in FAPs (Figure 7C)."
BAP1 affects RING finger domain
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7
sparser
"Recombinant importin-αs and TNPO1 were expressed in Escherichia coli and purified to homogeneity to investigate their interactions with the CTD of BAP1 (residues 596–729) fused with a maltose-binding protein (MBP) tag (hereafter MBP-BAP1 CTD ) by size-exclusion chromatography (SEC; xref )."
sparser
"In gastric cancer, DIM exerts antitumor effects through multiple mechanisms: Induction of ferroptosis via the BAP1-IP3R axis [ xref ]; STIM1-mediated store-operated calcium entry leading to cell death [ xref ]; inhibition of proliferation and induction of apoptosis via the TRAF2-p38 signaling pathway [ xref ]; potentiation of paclitaxel’s antitumor effects through the Akt/FOXM1 signaling cascade [ xref ]; suppression of cell growth via Hippo signaling pathway activation [ xref ]; activation of the aryl hydrocarbon receptor pathway, promoting its nuclear translocation, inducing apoptosis, delaying cell cycle progression, and inhibiting proliferation [ xref ]."
reach
"Prominent among the positively enriched gene sets were those related to writers of histone H3K27Me3, including PRC2 and SUZ12 (XREF_FIG), as well as genes participating in cell proliferation and transcription regulation involving ubiquitin signaling mediated by the Bap1, HCF1, and YY1 complex, EED related stem cell pluripotency, cytokine signaling, and cell adhesion; 100 of the top pathways differentially affected in MMs from TKO versus DKO mice are presented in XREF_SUPPLEMENTARY."
reach
"Our RNA-seq analysis revealed that MMs from Bap1; Nf2; Cdkn2a CKO mice exhibit positively enriched gene sets consistent with cellular processes previously implicated in Bap1 function, such as genes mediated by the Bap1, HCF1, and YY1 complex, which play a role in cellular proliferation and transcription regulation involving ubiquitin signaling."
BAP1 affects H2AK119ub1
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7
reach
"Until recently, the combination of pemetrexed and cisplatin was the only approved first-line therapy, yielding a median overall survival (OS) of 12.1 months.2 Nivolumab plus ipilimumab was approved recently as initial treatment for malignant pleural mesothelioma (MPM) on the basis of a phase 3 clinical trial that resulted in a median OS of 18.1 months.3 4 There are no approved therapies for patients with tumor relapse after first-line therapies.Risk factors in developing mesothelioma include exposure to asbestos5 and other carcinogenic fibers such as erionite,6 and previous radiation therapy.7 8 Studies of familial clusters of mesothelioma have revealed genetic predisposition to develop MM.9 10 Recent work has identified germline mutations in BAP1 that can predispose to mesothelioma11 12 and other cancers such as uveal and cutaneous melanoma, basal cell carcinoma, meningioma, and renal cell cancers.13 14 We previously identified deleterious germline mutations in 12% of 241 consecutive patients with MM who enrolled on a prospective natural history study, with BAP1 being the most frequent germline mutation.15
BAP1 was also recurrently inactivated at the somatic level, suggesting BAP1 variants undergoing positive selection in the context of the classic “two-hit” model.BAP1, a nuclear deubiquitylase, was initially discovered as an interaction partner of the tumor suppressor BRCA1.16 Subsequent studies revealed that BAP1 binds to BARD1, which, in turn, binds to BRCA1, forming the BRCA1-BARD1-BAP1 complex that is crucial for the homologous recombination (HR)–mediated repair of DNA double-strand breaks (DSBs).17 PARP enzymes play a major role in DNA single-strand break repair and base excision repair pathways."
sparser
"That study highlighted the role of coding and non-coding genes that were differentially expressed between SCNA subtypes of monosomy 3 uveal melanomas that were associated with metastasis. xref Five genes have been reported to be frequently mutated in uveal melanoma. xref Mutations in GNAQ and GNA11 occur early in tumor formation while BAP1 , SF3B1 , and EIF1AX mutations likely occur later in tumor progression. xref Mutation in EIF1AX is an indicator of good prognosis, whereas mutations in SF3B1 and BAP1 are associated with intermediate and poor prognosis."
sparser
"To further investigate the genetic interaction between BAP1 and SF3B1 mutations and to exclude that other alterations in Mel202 might contribute to the incompatibility with BAP1 deletion, we asked whether deletion of the SF3B1 ‐mutant allele in Mel202 cells could reverse BAP1 KO‐induced growth arrest."
sparser
"The Rotterdam Ocular Melanoma Study Group investigated the association of EIF1AX , SF3B1 and BAP1 mutation with disease-free survival and metastatic risk of patients with uveal melanoma. xref In their recent article, they published a Kaplan-Meier survival probability curve regarding these mutations."
sparser
"Uveal melanoma (UM) is a relative rare disease and has a high mortality rate due to metastasis in about half of all patients within 15 y after diagnosis. xref , xref , xref It is the most common primary intra‐ocular malignancy in adults in the Western world. xref UM specific mutations in the alpha subunit genes GNAQ and GNA11 are described as well as mutations in BAP1 , SF3B1 , and EIF1AX . xref , xref , xref Mutations in the latter 3 genes are found in ∼75% of all UM and are useful for prognostication of patients. xref , xref , xref BAP1 ‐mutated UM gives rise to early‐onset metastasis whereas SF3B1 ‐mutated UM gives rise to late‐onset metastasis and EIF1AX ‐mutated UM hardly metastasizes. xref Mutations in PLCB4 and CYSLTR2 are described in UM in a mutually exclusive manner to GNAQ or GNA11 mutations but so far have not been associated with prognosis. xref , xref Copy number alterations in chromosomes 1, 3, 6, and 8 are correlated with prognosis of the UM patient. xref , xref UM with EIF1AX , SF3B1 and BAP1 mutations are associated with unique chromosomal patterns, suggesting distinct UM subclasses."
N1ICD affects BAP1
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6
MED1 affects BAP1
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6
2
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1
2
BAP1 affects inflammatory response
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6
BAP1 inhibits inflammatory response.
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3
BAP1 activates inflammatory response.
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3
BAP1 affects gemcitabine
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6
sparser
"That study highlighted the role of coding and non-coding genes that were differentially expressed between SCNA subtypes of monosomy 3 uveal melanomas that were associated with metastasis. xref Five genes have been reported to be frequently mutated in uveal melanoma. xref Mutations in GNAQ and GNA11 occur early in tumor formation while BAP1 , SF3B1 , and EIF1AX mutations likely occur later in tumor progression. xref Mutation in EIF1AX is an indicator of good prognosis, whereas mutations in SF3B1 and BAP1 are associated with intermediate and poor prognosis."
sparser
"To further investigate the genetic interaction between BAP1 and SF3B1 mutations and to exclude that other alterations in Mel202 might contribute to the incompatibility with BAP1 deletion, we asked whether deletion of the SF3B1 ‐mutant allele in Mel202 cells could reverse BAP1 KO‐induced growth arrest."
sparser
"The Rotterdam Ocular Melanoma Study Group investigated the association of EIF1AX , SF3B1 and BAP1 mutation with disease-free survival and metastatic risk of patients with uveal melanoma. xref In their recent article, they published a Kaplan-Meier survival probability curve regarding these mutations."
sparser
"Uveal melanoma (UM) is a relative rare disease and has a high mortality rate due to metastasis in about half of all patients within 15 y after diagnosis. xref , xref , xref It is the most common primary intra‐ocular malignancy in adults in the Western world. xref UM specific mutations in the alpha subunit genes GNAQ and GNA11 are described as well as mutations in BAP1 , SF3B1 , and EIF1AX . xref , xref , xref Mutations in the latter 3 genes are found in ∼75% of all UM and are useful for prognostication of patients. xref , xref , xref BAP1 ‐mutated UM gives rise to early‐onset metastasis whereas SF3B1 ‐mutated UM gives rise to late‐onset metastasis and EIF1AX ‐mutated UM hardly metastasizes. xref Mutations in PLCB4 and CYSLTR2 are described in UM in a mutually exclusive manner to GNAQ or GNA11 mutations but so far have not been associated with prognosis. xref , xref Copy number alterations in chromosomes 1, 3, 6, and 8 are correlated with prognosis of the UM patient. xref , xref UM with EIF1AX , SF3B1 and BAP1 mutations are associated with unique chromosomal patterns, suggesting distinct UM subclasses."
BAP1 affects N1ICD
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6
BAP1 affects Mesenchymal Stem Cells
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6
BAP1 affects MED1
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6
BAP1 affects Deubiquitinase
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6
BAP1 deubiquitinates Deubiquitinase.
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3
BAP1 activates Deubiquitinase.
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3
BAP1 activates Deubiquitinase. 3 / 3
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3
reach
"In addition to TFs, SLC7A11 transcription is also repressed by BRCA1-associated protein 1 (BAP1) – a major component of a deubiquitinase (DUB) complex which catalyzes deubiquitination of histone 2 A (H2A) associated with the SLC7A11 promoter.96 Not surprisingly, BAP1 promotes ferroptosis in a DUB-dependent manner."
BAP1 affects Carcinoma, Renal Cell
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6
BAP1 inhibits Carcinoma, Renal Cell.
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4
BAP1 activates Carcinoma, Renal Cell.
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2
BAP1 activates Carcinoma, Renal Cell. 2 / 2
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2
reach
"On the other hand, the occasionally described heterozygous deletions of these genes cannot be completely excluded in our series, because NGS procedure and mode of data analysis were not sensitive to moderate CNV (copy number variation), the detection of which was not the aim of this panel.Germline mutations in BAP1 are known to underlie sometimes melanomas, renal cell carcinomas, malignant mesotheliomas, and some other cancers [31]."
sparser
"Considering the frequent mutations and deletions of the TP53 gene in human cancers, the stabilization of pVHL by the UFL1-BAP1 axis might be particularly important in cancer cells harboring TP53 mutant or loss, such as CRC cells (SW620 and HCT116 with p53 KO) and pancreatic cancer cells (AsPC-1) (fig."
reach
"p53 binds to the SLC7A11 promoter, directly suppressing its transcription; the nuclear deubiquitinase (DUB) BAP1 represses SLC7A11 transcription by removing histone 2A ubiquitination from the SLC7A11 promoter; and KEAP1 represses SLC7A11 transcription through degrading NRF2, a master transcription factor of antioxidant response and regulator of SLC7A11."
reach
"In this study, we found that hypoxia-induced BAP1 enhances erastin-induced ferroptosis in NPC by stabilizing H2A.Studies have shown that many tumor cells under a hypoxic microenvironment are less sensitive to chemotherapeutic agents because these agents typically require oxygen for maximum activity [12]."
E3_Ub_ligase affects BAP1
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5
E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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3
sparser
"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
E3_Ub_ligase binds BAP1. 2 / 2
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2
CRISPR affects BAP1
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5
reach
"B. Artegiani et al. described that liver organoids with four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, and NF1) gained malignancy after loss-of-function of BAP1 by CRISPR/Cas9, because BAP1 could control the expression of junctional and cytoskeleton components by regulating chromatin accessibility (44)."
BAP1 affects signal transduction
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5
Mutated BAP1 inhibits signal transduction. 5 / 5
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5
reach
"These previous studies can support our finding that BAP1 mutations causing loss of BAP1 expression could induce the immunosuppressive microenvironment in UM.Mechanistically, we demonstrated in the current study that BAP1 mutations could inhibit the NF-κB signaling pathway, thereby repressing the cytokine secretion and antigen presentation by macrophages and inducing immunosuppressive microenvironment in UM."
reach
"A preliminary conclusion can be drawn in the current study that BAP1 mutations might repress the NF-κB signaling pathway, which repressed the cytokine secretion and antigen presentation by macrophages, inducing the immunosuppressive microenvironment, augmenting the malignant phenotypes of UM cells and ultimately promoting the growth and metastasis of UM (Fig. 10)."
reach
"BAP1 mutations may inhibit the NF-kappaB signaling pathway, repressing the cytokine secretion and antigen presentation by macrophages, which induces the immunosuppressive microenvironment, enhances the malignant phenotypes of UM cells and ultimately promotes the growth and metastasis of UM."
sparser
"Considering the frequent mutations and deletions of the TP53 gene in human cancers, the stabilization of pVHL by the UFL1-BAP1 axis might be particularly important in cancer cells harboring TP53 mutant or loss, such as CRC cells (SW620 and HCT116 with p53 KO) and pancreatic cancer cells (AsPC-1) (fig."
reach
"Moreover, as revealed by western blot assay, knockdown of BAP1 also upregulated the expression of GPX4 reduced by LPS (Fig. 5H and I; CON vs. LPS, p = 0.002; NC(-) vs. BAP1(-), p = 0.004) and downregulated the expression of ASCL4 elevated by LPS (Fig. 5H and J; CON vs. LPS, p = 0.002; NC(-) vs. BAP1(-), p = 0.01), which were the marker proteins of ferroptosis."
reach
"For example, differentiation to mature neurons and glia could require antagonism of PRC-mediated transcriptional repression.We were thus intrigued by our serendipitous discovery that Bap1 deletion in ENS lineages caused profound bowel dysfunction and early death in mice, mimicking human nCIPO or HSCR physiology."
BAP1 affects DNA replication
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5
BAP1 affects ASXL1/2
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4
1
reach
"HG inhibits cystine uptake in podocytes by promoting the expression of BAP1 and inhibiting H2Aub deubiquitination on SLC7A11, a functional protein targeting cystine transporter system Xc-on the cell membrane, leading to the deposition of lipid peroxides and the occurrence of ferroptosis in podocytes."
reach
"Taken together, we concluded that Bap1 directly binds SMN and prevents SMN degradation by posttranslational deubiquitination of SMN.Since a lysine residue is one of the predominant targets for ubiquitination, we examined which of the lysine residues in SMN is critical for its ubiquitin-dependent degradation by introducing a non-lysine mutation on phylogenetically conserved lysine residues (Supplemental Figure 8A)."
reach
"These results indicate that Bap1 posttranscriptionally regulates SMN levels and thus affects the function of SMN in FAPs.To test the direct interaction between Bap1 and SMN, we performed endogenous reciprocal immunoprecipitation experiments using freshly isolated FAPs and revealed that Bap1 directly binds SMN in FAPs (Figure 7C)."
PRC2_complex affects BAP1
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4
BAP1 binds PRC2_complex. 4 / 4
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4
sparser
"ASXL1 functions in transcriptional repression through its interaction with PRC2 and BAP1. xref BCORL1 is a transcriptional co-repressor that interacts with PCGF1, a core complex of the PRC1.1 complex. xref The RUNX1-CBF-b heterodimer mediates transcription by binding to RUNX sites, but also represses transcription by interacting and recruiting BMI1 of the PRC1 complex to target sites. xref IKZF1 regulates transcription by interacting with repressive epigenetic complexes such as HDAC1, HDAC2, CHD3, CHD4, and SWI/SNF complex, and also recruits PRC2 to target gene loci in T cells. xref Thus, while the commonly mutated genes in CML have their own exclusive roles in transcriptional regulation, they also share a striking commonality as modulators of the PRC."
sparser
"Given that the composition and expression of PRC1 and BAP1 complexes changes extensively during development ( xref ; xref , xref ; xref ; xref ), in future work, it will be interesting to investigate how the balance between these two opposing activities is regulated at different developmental stages and how cell type-specific H2AK119ub1 levels influence the transcriptional potential of the genome."
sparser
"Recent CRISPR screening studies by Dixit’s group further identified that depletion of PRC1 subunit Ring1B (but not Ring1A) could rescue the cell death induced by loss of BAP1 xref , indicating that there is a robust and direct epigenetic dynamic occurring between the PRC1 and BAP1 complexes that require a balanced state to properly regulate gene expression and determine cell fate."
sparser
"PRC1 regulates SLC7A11 expression and H2Aub occupancy on the SLC7A11 promoter. (a) ChIP–qPCR showing the binding of BMI-1 and H2Aub on the SLC7A11 promoter, and decreased binding of H2Aub on the SLC7A11 promoter upon BMI-1 knockdown. (b) ChIP– qPCR showing the binding of RNF2 and H2Aub on the SLC7A11 promoter, and decreased binding of H2Aub on the SLC7A11 promoter upon RNF-2 knockdown. (c-f) BMI-1 or RNF2 deficiency increased SLC7A11 mRNA (c, d) and protein levels (e, f) in UMRC6 cells. (g-h) BMI-1 (g) or RNF2 (h) deficiency in 786-O cells increased SLC7A11 mRNA levels. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.
lines used in our study identified all these PR-DUB components but failed to identify any PRC1 component as BAP1-interacting proteins, arguing against a physical interaction between BAP1 and PRC1."
sparser
"Several studies and clinical trials [ xref ], have shown that PARP inhibitors influence cancers in which mutations in BRCA1 or BRCA2 are observed, which led us to assume that the cancerous growth-inhibiting interaction of BAP1 with BRCA1 may already be perturbed in this case, and that PARP inhibitors may actually be blocking the novel interaction of BAP1 with PARP3 which enhances cancer growth."
Malignant Mesothelioma affects BAP1
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4
Malignant Mesothelioma binds BAP1. 4 / 4
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4
sparser
"BAP1 knockdown in MM cell lines has been paradoxically associated to a decreased proliferation, with an accumulation of cells in the S phase of the cell cycle xref , suggesting that BAP1 loss might promote tumorigenesis inducing a delayed, but more permissive, G1/S checkpoint xref ."
MP65 affects BAP1
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4
H2AK119Ub affects BAP1
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4
sparser
"Broader applicability of PRC2 inhibition to the treatment of other cancers is supported by the general prevalence of mutations in other chromatin-associated proteins that perturb the balance of activities regulating H3K27me3, including components of the SWI/SNF chromatin remodeling complex and the BAP1 H2A deubiquitinase complex ( xref )."
BAP1 affects radioresistance
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4
BAP1 affects mutations
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4
BAP1 affects biosynthetic process
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4
BAP1 activates biosynthetic process. 4 / 4
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4
reach
"The large number of genome editing tools and techniques available for E. coli [60,61] allow quick and precise manipulation of this organism for biotechnological applications.In the context of NP biosynthesis in E. coli, metabolic engineering has been used to build chassis strains such as HM0079 and BAP1, that are optimized to support the synthesis of complex NPs by expressing phosphopantetheine transferase, an enzyme crucial for the function of the polyketide synthases and nonribosomal peptide synthetases [9,10]."
reach
"rTRAIL sensitivity of the parental BAP1-null H226 MM line was significantly diminished following expression of wild-type BAP1 and each of the mutant constructs except those with an inactive deubiquitinating or ASXL protein binding site (XREF_FIG), implicating the function of these sites in BAP1 induced TRAIL resistance."
sparser
"Given that the composition and expression of PRC1 and BAP1 complexes changes extensively during development ( xref ; xref , xref ; xref ; xref ), in future work, it will be interesting to investigate how the balance between these two opposing activities is regulated at different developmental stages and how cell type-specific H2AK119ub1 levels influence the transcriptional potential of the genome."
sparser
"Recent CRISPR screening studies by Dixit’s group further identified that depletion of PRC1 subunit Ring1B (but not Ring1A) could rescue the cell death induced by loss of BAP1 xref , indicating that there is a robust and direct epigenetic dynamic occurring between the PRC1 and BAP1 complexes that require a balanced state to properly regulate gene expression and determine cell fate."
sparser
"PRC1 regulates SLC7A11 expression and H2Aub occupancy on the SLC7A11 promoter. (a) ChIP–qPCR showing the binding of BMI-1 and H2Aub on the SLC7A11 promoter, and decreased binding of H2Aub on the SLC7A11 promoter upon BMI-1 knockdown. (b) ChIP– qPCR showing the binding of RNF2 and H2Aub on the SLC7A11 promoter, and decreased binding of H2Aub on the SLC7A11 promoter upon RNF-2 knockdown. (c-f) BMI-1 or RNF2 deficiency increased SLC7A11 mRNA (c, d) and protein levels (e, f) in UMRC6 cells. (g-h) BMI-1 (g) or RNF2 (h) deficiency in 786-O cells increased SLC7A11 mRNA levels. *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****, p < 0.0001.
lines used in our study identified all these PR-DUB components but failed to identify any PRC1 component as BAP1-interacting proteins, arguing against a physical interaction between BAP1 and PRC1."
sparser
"Several studies and clinical trials [ xref ], have shown that PARP inhibitors influence cancers in which mutations in BRCA1 or BRCA2 are observed, which led us to assume that the cancerous growth-inhibiting interaction of BAP1 with BRCA1 may already be perturbed in this case, and that PARP inhibitors may actually be blocking the novel interaction of BAP1 with PARP3 which enhances cancer growth."
BAP1 affects Osteosarcoma
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4
BAP1 inhibits Osteosarcoma. 4 / 4
|
4
reach
"In this study, the roles of BAP1 in potential targets, biological functions, signaling pathways, and immune infiltration were comprehensively explored by mining the osteosarcoma datasets from GEO and TARGET databases using the rapidly developing bioinformatics in recent years.In summary, through bioinformatics and in vitro assays, this study demonstrated that BAP1 was a tumor suppressor in osteosarcoma and provided new clues for osteosarcoma treatment such as BAP1-targeted therapy."
reach
"BINs are highly penetrant, present in up to 90% of mutation carriers, and typically present as multiple, skin colored or reddish-brown, dome-shaped melanocytic tumors (also or previously called BAP1-inactivlated melanocytic tumors, Wiesner nevi, BAPomas, nevoid melanoma-like melanocytic proliferations, BAP1 mutant Spitz nevi, and melanocytic BAP1-mutated atypical intradermal tumors)."
reach
"Morphology of this secondary clone strictly depends on the type of second genetic hit: inactivation of the BAP1 (BRCA1-associated protein) gene is the hallmark of BAP1-inactivated nevus (BIN) (33, 34); gain-of-function mutations of CTNNB1 or loss of APC is found in deep penetrating nevus (DPN) (35, 36); loss-of-function of PRKAR1A is typical of pigmented epithelioid melanocytoma (PEM) (37, 38)."
BAP1 affects Meningioma
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4
BAP1 affects MP65
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4
reach
"Furthermore, we also demonstrated that hyperactivity of ERK1/2 and JNK/c-Jun signaling induced by BAP1 downregulation was necessary for ICC cell proliferation, cell cycle progression, and invasion in vitro and in vivo using the inhibitors of the ERK1/2 pathway (U0126) and JNK/c-Jun pathway (SP600125)."
reach
"Partially consistent with our results, BAP1 was unfolded to increase the COX-2 and mPGES-1 expression by activating the NF-κB signaling pathway and inducing the release of IL-1β (Viana et al. 2020), but this study failed to explore the regulatory role of BAP1 mutations on the NF-κB signaling pathway."
reach
"Taken together, our findings show that the metalloprotease BaP1 directly activates FLSs to produce PGE by a COX-2-dependent mechanism involving the coupling of the inducible enzymes COX-2 and mPGES-1 and intracellular PLA s. BaP1 also induced release of IL-1β, which up-regulates the production of PGE at a later stage of the stimulation."
sparser
"Broader applicability of PRC2 inhibition to the treatment of other cancers is supported by the general prevalence of mutations in other chromatin-associated proteins that perturb the balance of activities regulating H3K27me3, including components of the SWI/SNF chromatin remodeling complex and the BAP1 H2A deubiquitinase complex ( xref )."
BAP1 affects Carcinoma, Basal Cell
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4
reach
"We found an obvious increase in the total extent of H2AK119Ub in Bap1-KO MC38 cells compared to WT cells (Fig. 1f) and re-expression of WT human BAP1 but not a catalytical inactive BAP1 Cys91-Ala (C91A) variant [18] in Bap1-KO cells rescued both cell-surface PD-L1 accumulation levels and Cd274 mRNA expression (Fig. 1j, k), indicating that Bap1-mediated regulation of PD-L1 expression is dependent on its enzymatic activity."
sparser
"CoIP experiments in cells co-transfected with full length Myc-tagged BAP1 (Myc- BAP1 ) and Flag-tagged full-length HIF-1β, or HIF-1β fragments covering residues 2 to 470 [HIF-1β(2-470)], 142-470 [HIF-1β(142-470)], 471-789 [HIF-1β(471-789)], 582-789 [HIF-1β(592-789)] ( xref ), showed that BAP1 binds to the N terminus region of HIF-1β, specifically to the DNA binding and dimerization region [HIF-1β(2-470) and HIF-1β (142-470)] ( xref )."
BAP1 affects 6-dEB
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4
ASXL1 affects H2AK119Ub
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4
sparser
"CoIP experiments in cells co-transfected with full length Myc-tagged BAP1 (Myc- BAP1 ) and Flag-tagged full-length HIF-1β, or HIF-1β fragments covering residues 2 to 470 [HIF-1β(2-470)], 142-470 [HIF-1β(142-470)], 471-789 [HIF-1β(471-789)], 582-789 [HIF-1β(592-789)] ( xref ), showed that BAP1 binds to the N terminus region of HIF-1β, specifically to the DNA binding and dimerization region [HIF-1β(2-470) and HIF-1β (142-470)] ( xref )."
Transcriptional regulator affects BAP1
|
3
reach
"As already discussed, a strong reduction in the expression of the Bap1
exons was demonstrated in the RNA-seq datasets from Bap1
Cγ1-cre relative to control GC B cells (
Supplementary Figures S3C, D
), confirming an effective Cre-mediated Bap1 gene inactivation in the cells captured for the RNA-seq."
reach
"Again, Bap1
Cγ1-Cre B cells demonstrated normal levels of class switching over 4 days in culture (
Supplementary Figures S6A, B
), though Cre-mediated Bap1
to Bap1
allele conversion was observed as early as days 3, albeit without full loss of the Bap1
allele (
Supplementary Figures S6C, D
)."
Bisphenol A affects BAP1
3
|
sparser
"The Rotterdam Ocular Melanoma Study Group investigated the association of EIF1AX , SF3B1 and BAP1 mutation with disease-free survival and metastatic risk of patients with uveal melanoma. xref In their recent article, they published a Kaplan-Meier survival probability curve regarding these mutations."
sparser
"Uveal melanoma (UM) is a relative rare disease and has a high mortality rate due to metastasis in about half of all patients within 15 y after diagnosis. xref , xref , xref It is the most common primary intra‐ocular malignancy in adults in the Western world. xref UM specific mutations in the alpha subunit genes GNAQ and GNA11 are described as well as mutations in BAP1 , SF3B1 , and EIF1AX . xref , xref , xref Mutations in the latter 3 genes are found in ∼75% of all UM and are useful for prognostication of patients. xref , xref , xref BAP1 ‐mutated UM gives rise to early‐onset metastasis whereas SF3B1 ‐mutated UM gives rise to late‐onset metastasis and EIF1AX ‐mutated UM hardly metastasizes. xref Mutations in PLCB4 and CYSLTR2 are described in UM in a mutually exclusive manner to GNAQ or GNA11 mutations but so far have not been associated with prognosis. xref , xref Copy number alterations in chromosomes 1, 3, 6, and 8 are correlated with prognosis of the UM patient. xref , xref UM with EIF1AX , SF3B1 and BAP1 mutations are associated with unique chromosomal patterns, suggesting distinct UM subclasses."
ODN affects BAP1
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3
NCIT:C94600 affects BAP1
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3
GZ17-6.02 affects BAP1
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3
reach
"Hence, our discovery that GZ17-6.02 is enhancing BAP1 expression favors increased expression from the wild type unmutated BAP1 allele in uveal melanoma cells.GZ17-6.02 changed the methylation and acetylation of Histone H3 in uveal melanoma cells, most notably, the mono-methylation of lysine 9 and lysine 4 was reduced and this correlated with a trend for increased di-methylation of lysine 4."
GEP affects BAP1
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3
sparser
"Inactivating mutations in the tumor suppressor BAP1 are associated with the class 2 GEP and high metastatic risk xref , whereas single nucleotide substitutions in SF3B1 and EIF1AX are found mainly in class 1 tumors and are associated with intermediate and low metastatic risk, respectively xref , xref ."
sparser
"The Rotterdam Ocular Melanoma Study Group investigated the association of EIF1AX , SF3B1 and BAP1 mutation with disease-free survival and metastatic risk of patients with uveal melanoma. xref In their recent article, they published a Kaplan-Meier survival probability curve regarding these mutations."
sparser
"Uveal melanoma (UM) is a relative rare disease and has a high mortality rate due to metastasis in about half of all patients within 15 y after diagnosis. xref , xref , xref It is the most common primary intra‐ocular malignancy in adults in the Western world. xref UM specific mutations in the alpha subunit genes GNAQ and GNA11 are described as well as mutations in BAP1 , SF3B1 , and EIF1AX . xref , xref , xref Mutations in the latter 3 genes are found in ∼75% of all UM and are useful for prognostication of patients. xref , xref , xref BAP1 ‐mutated UM gives rise to early‐onset metastasis whereas SF3B1 ‐mutated UM gives rise to late‐onset metastasis and EIF1AX ‐mutated UM hardly metastasizes. xref Mutations in PLCB4 and CYSLTR2 are described in UM in a mutually exclusive manner to GNAQ or GNA11 mutations but so far have not been associated with prognosis. xref , xref Copy number alterations in chromosomes 1, 3, 6, and 8 are correlated with prognosis of the UM patient. xref , xref UM with EIF1AX , SF3B1 and BAP1 mutations are associated with unique chromosomal patterns, suggesting distinct UM subclasses."
E3_Ub_ligase affects BARD1
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3
E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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3
sparser
"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
COPI complex affects BAP1
|
3
reach
"Overall, the loss of mass of COPA on blot could not be tied to the loss of ubiquitin and additional experiments are required to explain this observation.To exclude that the BAP1 interaction with the COPI complex is an artifact of overexpression of the exogenous BAP1 construct, we immunoprecipitated endogenous BAP1 using different antibodies against BAP1 in cell lysate from HeLa FRT parental cells (Fig 5D)."
| PMC
BARD1 affects E3_Ub_ligase
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E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
BAP1 affects ubiquitins
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BAP1 affects transcriptional regulator
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BAP1 affects response to stress
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BAP1 inhibits response to stress. 3 / 3
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"BAP1 loss in UM leads to ASXL2 reduction and lipid homeostasis dysregulation, conferring lipotoxicity resistance and an enhanced oxidative stress response—an adaptation that can be exploited with atorvastatin, which induces lipid peroxidation and cell death specifically in BAP1‐mutant liver metastases (Figure 6)."
BAP1 affects regulation of cell cycle
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BAP1 inhibits regulation of cell cycle. 3 / 3
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"Their studies revealed differential expression of the cancer-related lncRNAs Malat1, Neat1, H19, Meg3, and their associated miRNA-target pairs, regulating various hallmarks of tumorigenesis such as cell cycle and p53 signaling.BRCA1-Associated Protein 1 (BAP1) is known to enhance BRCA1 tumor suppressor potential and its inactivation is associated with various cancers, in particular clear-cell renal cell carcinoma (ccRCC)."
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BAP1 affects mastoparan-M
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BAP1 affects laminin
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BAP1 affects homeostatic process
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BAP1 affects erastin
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BAP1 affects cytokine production
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Mutated BAP1 inhibits cytokine production. 3 / 3
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"BAP1 mutations may inhibit the NF-kappaB signaling pathway, repressing the cytokine secretion and antigen presentation by macrophages, which induces the immunosuppressive microenvironment, enhances the malignant phenotypes of UM cells and ultimately promotes the growth and metastasis of UM."
BAP1 affects TG2-179-1
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BAP1 affects Recurrence
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BAP1 activates Recurrence. 3 / 3
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"Furthermore, BAP1 has been demonstrated to increase the risk of disease recurrence in patients with resected localized disease: in a cohort of 1479 patients, those with BAP1 loss of function (10.3%) had worse relapse-free survival, even after statistical adjustment for the UISS risk score [49]."
reach
"XREF_BIBR Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 non metastatic RCC cases treated with nephrectomy : BAP1 was negative in 82 of 559 tumors (14.7%), and Cox regression indicated a significantly worse disease-free and overall survival for patients negative for BAP1 protein compared to patients with BAP1 positive tumors."
BAP1 affects Proteasome
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BAP1 affects Neuroblastoma
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"In this study, we found that hypoxia-induced BAP1 enhances erastin-induced ferroptosis in NPC by stabilizing H2A.Studies have shown that many tumor cells under a hypoxic microenvironment are less sensitive to chemotherapeutic agents because these agents typically require oxygen for maximum activity [12]."
BAP1 affects Lymphoma, B-Cell
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BAP1 inhibits Lymphoma, B-Cell. 3 / 3
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"However, the loss of BAP1 leads to a substantial acceleration of B cell lymphoma cell growth in immunocompetent mice, indicating that BAP1 may function as a tumor suppressor via regulating TME and tumor immune response in this context.Decrease or loss of MHC-II expression in B cell lymphoma has been associated with genetic alterations, such as CIITA deficiency, and is associated with poor survival in human B cell lymphoma."
BAP1 affects Hemorrhage
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"Additionally, reconstitution of BAP1 into the BAP1-KO cells downregulated H3K27me3 and EZH2 (Fig. 2c), suggesting that BAP1 loss might upregulate H3K27me3 and EZH2 and activate their downstream signaling.A recent study indicated that BAP1 is localized in the endoplasmic reticulum (ER) and bound to the type 3 inositol 1, 4, and 5-triphosphate receptor (IP3R3) [22]."
BAP1 affects GEP
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"Inactivating mutations in the tumor suppressor BAP1 are associated with the class 2 GEP and high metastatic risk xref , whereas single nucleotide substitutions in SF3B1 and EIF1AX are found mainly in class 1 tumors and are associated with intermediate and low metastatic risk, respectively xref , xref ."
sparser
"The Rotterdam Ocular Melanoma Study Group investigated the association of EIF1AX , SF3B1 and BAP1 mutation with disease-free survival and metastatic risk of patients with uveal melanoma. xref In their recent article, they published a Kaplan-Meier survival probability curve regarding these mutations."
sparser
"Uveal melanoma (UM) is a relative rare disease and has a high mortality rate due to metastasis in about half of all patients within 15 y after diagnosis. xref , xref , xref It is the most common primary intra‐ocular malignancy in adults in the Western world. xref UM specific mutations in the alpha subunit genes GNAQ and GNA11 are described as well as mutations in BAP1 , SF3B1 , and EIF1AX . xref , xref , xref Mutations in the latter 3 genes are found in ∼75% of all UM and are useful for prognostication of patients. xref , xref , xref BAP1 ‐mutated UM gives rise to early‐onset metastasis whereas SF3B1 ‐mutated UM gives rise to late‐onset metastasis and EIF1AX ‐mutated UM hardly metastasizes. xref Mutations in PLCB4 and CYSLTR2 are described in UM in a mutually exclusive manner to GNAQ or GNA11 mutations but so far have not been associated with prognosis. xref , xref Copy number alterations in chromosomes 1, 3, 6, and 8 are correlated with prognosis of the UM patient. xref , xref UM with EIF1AX , SF3B1 and BAP1 mutations are associated with unique chromosomal patterns, suggesting distinct UM subclasses."
BAP1 affects Cholangiocarcinoma
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BAP1 affects COPI complex
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"Overall, the loss of mass of COPA on blot could not be tied to the loss of ubiquitin and additional experiments are required to explain this observation.To exclude that the BAP1 interaction with the COPI complex is an artifact of overexpression of the exogenous BAP1 construct, we immunoprecipitated endogenous BAP1 using different antibodies against BAP1 in cell lysate from HeLa FRT parental cells (Fig 5D)."
| PMC
reach
"The tumour was histopathologically atypical because of the presence of confluent pleomorphism, solid sheets of cells and grouped mitotic figures : these features were consistent with a melanocytic neoplasm with intermediate morphology (' BAP1 inactivated melanocytoma '; BIM) between a BAP1 inactivated melanocytic naevus and a BAP1 inactivated melanoma."
BAP1 affects BARD1, and E3_Ub_ligase
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E3_Ub_ligase binds BAP1 and BARD1. 3 / 3
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"According to this hypothesis, Nishikawa et al showed that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of the BRCA1/BARD1 complex, and that BAP1 and BRCA1/BARD1 mutually regulate ubiquitination in the cell cycle and in the DNA damage response pathway. xref According to the present state of knowledge, it is reasonable to speculate that BAP1 may exert a regulatory role in the DNA damage response."
BAP1 affects ASXL proteins
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ASXL proteins affects BAP1
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Small interfering RNA affects BAP1
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MiR-31-5p affects BAP1
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Hsa-miR-200c-3p affects BAP1
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Fluoranthene affects BAP1
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Fluoranthene activates BAP1. 2 / 2
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"BAP-1 induced by fluoranthene comparative proteomic analysis was performed on proteins extracted from fluoranthene exposed cells on 1 d, 3 d, 6 d and 8 d compared with control cells using isobaric tags for relative and absolute quantization (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins."
Ferroptosis affects BAP1
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Ferroptosis activates BAP1. 2 / 2
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Circ_0087851 affects BAP1
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"A study reported that BAP1 interacts directly with and localizes to γ-tubulin during mitosis and that BAP1 stabilizes γ-tubulin via deubiquitination to support microtubule nucleation and mitotic spindle assembly, thereby ensuring chromosome segregation and preventing chromosome abnormalities."
Reactive Oxygen Species affects BAP1
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Reactive Oxygen Species increases the amount of BAP1. 2 / 2
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ODN- affects BAP1
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"However, whether BAP1 can positively regulate the transcription of RHOJ via removing the monoubiquitination of histone H2A remains to be further delineated.Regarding the regulation of BAP1 at the transcriptional level in HCC, we identified two transcription factors, CTCF and NRF1, which positively regulated BAP1 transcription by direct binding to the promoter region of BAP1."
Mito-TEMPO affects BAP1
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"However, whether BAP1 can positively regulate the transcription of RHOJ via removing the monoubiquitination of histone H2A remains to be further delineated.Regarding the regulation of BAP1 at the transcriptional level in HCC, we identified two transcription factors, CTCF and NRF1, which positively regulated BAP1 transcription by direct binding to the promoter region of BAP1."
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"These results confirmed that the BPS construct efficiently induces genome edits in Bap1 and Pbrm1, but not in Setd2, in a dox-dependent manner.Upon confirming the genome editing we injected these ESCs into mouse blastocysts for tetraploid complementation and obtained nine founder BPS (Bap1-Pbrm1-Setd2) mice."
BAP1 affects γ-globin
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BAP1 affects vorinostat
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BAP1 affects phosphorylated-ERK1/2
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BAP1 affects pathogenesis
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BAP1 affects neutrophil chemotaxis
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BAP1 affects glutathione
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BAP1 increases the amount of glutathione. 2 / 2
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"The expression or activity of System X is affected by epigenetics, transcription, and posttranscriptional and posttranslational regulators, such as a tumor protein p53 (p53), the nuclear factor, erythroid 2-like 2 (NFE2L2), BRCA1-associated protein 1 (BAP1), or mucin 1 cell surface-associated (MUC1), leading to complex feedback mechanisms to control GSH levels in ferroptosis (Hayano et al., 2016; Chen et al., 2017; Song et al., 2018; Zhang Y. et al., 2018)."
BAP1 affects gluconeogenesis
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BAP1 activates gluconeogenesis. 2 / 2
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"Similarly , downregulation of BAP1 markedly increased cells in the S phase and reduced cells in the G0 / G1 phase , consistent with the results of a recent study that depletion of BAP1 resulted in a modest accumulation of host cell factor 1 , which promoted the transition from G1 to S phase41 ."
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Mutated BAP1 activates antigen processing and presentation. 2 / 2
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"BAP1 mutations may inhibit the NF-kappaB signaling pathway, repressing the cytokine secretion and antigen presentation by macrophages, which induces the immunosuppressive microenvironment, enhances the malignant phenotypes of UM cells and ultimately promotes the growth and metastasis of UM."
BAP1 affects Pancreatitis
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BAP1 activates Pancreatitis. 2 / 2
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"Although LOH of additional genes within Chr 3p21.1 may contribute to tumor suppression, and loss of BAP1 in pancreatic cancer may be secondary—rather than the cause of genomic instability—our mouse model suggests Bap1 ablation suffices to cause defective DNA repair, pancreatitis, and cooperates with oncogenic Kras to promote pancreatic cancer."
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"In fact this association with chromosome 3p loss has recently been strengthened by several publications demonstrating that 4 out of five ( VHL , PBRM1 , SETD2 and BAP1 ) of the most frequently mutated genes associated with CCRCC are on chromosome 3p xref – xref and that the mutation of either SETD2 , BAP1 or PBRM1 associates with poorer prognosis or progression in those patients xref , xref , xref ."
BAP1 affects Mitochondrial Proteins
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BAP1 affects Histone_H2B
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BAP1 deubiquitinates Histone_H2B. 2 / 2
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"Loss of Asx in flies led to an increase in Ub-H2A levels without influencing other chromatin marks (H3K4 me3, H3K27me3), and assays using purified proteins found Asx stimulates Calypso activity towards Ub-AMC, and that Asx and Calypso and the human orthologs BAP1 and ASXL1 deubiquitinate H2A but not H2B in reconstituted nucleosomes [XREF_BIBR]."
BAP1 affects HOXA genes
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BAP1 affects H3K27me3
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BAP1 affects H2AK119
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BAP1 affects DNA Breaks, Double-Stranded
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BAP1 affects DEUBAD
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BAP1 affects Chromosomal Instability
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BAP1 affects ASXH domain
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BAP1 affects ADAR2
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ASXL1 affects ASXH domain
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ADAR2 affects BAP1
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