IndraLab
Statements
reach
"Although the molecular genetics of cutaneous melanomas have been investigated in numerous studies [XREF_BIBR, XREF_BIBR, XREF_BIBR], the genetic events that lead to the development of CBN, MABN or ACBN are poorly understood and are limited to a few genes [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR], including BAP1 (BRCA1 binding protein 1), an oncogenic deubiquitinase, which has been found to be mutated in metastatic uveal melanomas and MABNs [XREF_BIBR]."
sparser
"Several lines of evidences indicate that PARP inhibitor administration might be an effective treatment in presence of BAP1 and/or RAD21 alterations since both BAP1 and RAD21 are involved in the DNA repair pathway, BAP1 interacts with BRCA1 and BRCA1-mediated DNA repair pathway alterations enhance the sensitivity to PARP inhibitor administration."
sparser
"Because of the involvement of RAD21 in the DNA repair pathway, the interaction of BAP1 with BRCA1 and the enhanced sensitivity to PARP inhibitor administration in presence of alterations in the BRCA1-mediated DNA repair pathway, it was decided first to treat the patient with FOLFIRI every 2 weeks [irinotecan 180 mg/m 2 , folinic acid 400 mg/m 2 , 5-fluorouracil (5-FU) 400 mg/m 2 intravenous infusion bolus, then 5-FU 2400 mg/m 2 intravenous infusion over 46 h] and then to start a PARP inhibitor."
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."
reach
"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."
| PMC
reach
"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."
sparser
"BAP1 is a 729 amino acid nuclear ubiquitin hydrolase with multiple functional domains and it has, therefore, been implicated in several cellular processes such as cell proliferation, DNA repair response, and chromatin dynamics. xref Specifically, an interaction between BAP1 and host cell factor 1 (HCF1), which interacts with histone-modifying complexes during cell division, has been described. xref More recently, it has been shown that BAP1, through an interaction with ASXL1 forms the polycomb group repressive deubiquitinase complex, which affects stem cell pluripotency. xref "
sparser
"BAP1 binds to HCF-1 in renal cancer cell lines. xref BAP1 binding was demonstrated through reciprocal immunoprecipitation experiments, and most BAP1 protein co-fractionated with HCF-1 by gel filtration chromatography. xref BAP1 binding to and co-fractionation with HCF-1 was also observed in orthotopic tumorgrafts in mice directly derived from surgically removed tumors of patients. xref Consistent with previous observations, xref immunoprecipitations of BAP1 and HCF-1 deplete BAP1 protein to a similar extent suggesting that most BAP1 is bound to HCF-1 (at least in cells reconstituted with BAP1). xref Binding to HCF-1 is important for BAP1-supression of cell proliferation. xref BAP1 reintroduction into two different BAP1-deficient ccRCC cell lines reduced cell growth. xref The inhibition of cell proliferation by BAP1 was compromised by disruption of the HCF-1 binding motif. xref Taken together these data suggest that BAP1 binding to HCF-1 is important for its tumor suppressor function in renal cancer."
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."
"The tumor suppressor BAP1 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, OGT and PCG1-α, preventing them from proteasomal degradation."
reach
"SETD2 is a histone H3 lysine 36 (H3K36) methyltransferase that regulates mRNA splicing and transcription elongation; BAP1 interacts with and deubiquitinates host cell factor-1 (HCF-1), a transcription co-activator, that regulates cell proliferation; and KDM5C a histone 3 trimethyl-lysine 4 (H3K4Me3) demethylase that erase active transcription marks."
BAP1 is modified
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BAP1 is phosphorylated.
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sparser
"As a fraction of the F679Lfs37X BAP1 mutant protein resides in the nucleus (Fig. xref , fourth lane from the right), even if much less abundant than in the cytoplasm, the remarkably increased p-S592 BAP1 signal of F679Lfs37X may just reflect the phosphorylation of the mutant BAP1 that has been localized in the nucleus from the beginning."
rlimsp
"Additionally, it was intriguing to find that phosphorylation of mutant BAP1 seemed to induce its translocation from the cytoplasm to the nucleus, as Western blot analysis detected strong p-S592 BAP1 in the nucleus of the mutant F679LfsX37-transduced cells (Fig.4d, second lane from the right)."
BAP1 is ubiquitinated.
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BAP1 is methylated.
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BAP1 is glycosylated.
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BAP1 affects cell population proliferation
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BAP1 inhibits cell population proliferation.
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BAP1 inhibits cell population proliferation. 10 / 50
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eidos
"Results BAP1 promotes proliferation in HNSCC cells regardless of HPV status Studies of the effects of BAP1 on cell proliferation have shown conflicting results , with some reporting that BAP1 suppresses cell proliferation ( 12 , 13 ) , and others reporting that BAP1 enhances proliferation ( 14 , 15 ) ."
sparser
"One intact allele of the BAP1 gene on chromosome 3 is requisite for the expression and translocation to the nucleus where BAP1 can inhibit tumor proliferation. xref Suppression of the nuclear localization of BAP1 (biallelic suppression) occurs in monosomy 3 because it is combined with assorted mutations on the remaining allele that may truncate the BAP1 protein, or affect nuclear localizer regions. xref BAP1 has definite additional prognostic value compared to the aforementioned tests and unlike the other prognostic tests permits microscopic confirmation of tumor."
Mutated BAP1 inhibits cell population proliferation. 1 / 1
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BAP1 activates cell population proliferation.
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BAP1 activates cell population proliferation. 10 / 29
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Mutated BAP1 activates cell population proliferation. 2 / 2
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BAP1 bound to ASXL1-MT activates cell population proliferation. 1 / 1
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reach
"Although the molecular genetics of cutaneous melanomas have been investigated in numerous studies [XREF_BIBR, XREF_BIBR, XREF_BIBR], the genetic events that lead to the development of CBN, MABN or ACBN are poorly understood and are limited to a few genes [XREF_BIBR, XREF_BIBR, XREF_BIBR - XREF_BIBR], including BAP1 (BRCA1 binding protein 1), an oncogenic deubiquitinase, which has been found to be mutated in metastatic uveal melanomas and MABNs [XREF_BIBR]."
sparser
"Several lines of evidences indicate that PARP inhibitor administration might be an effective treatment in presence of BAP1 and/or RAD21 alterations since both BAP1 and RAD21 are involved in the DNA repair pathway, BAP1 interacts with BRCA1 and BRCA1-mediated DNA repair pathway alterations enhance the sensitivity to PARP inhibitor administration."
sparser
"Because of the involvement of RAD21 in the DNA repair pathway, the interaction of BAP1 with BRCA1 and the enhanced sensitivity to PARP inhibitor administration in presence of alterations in the BRCA1-mediated DNA repair pathway, it was decided first to treat the patient with FOLFIRI every 2 weeks [irinotecan 180 mg/m 2 , folinic acid 400 mg/m 2 , 5-fluorouracil (5-FU) 400 mg/m 2 intravenous infusion bolus, then 5-FU 2400 mg/m 2 intravenous infusion over 46 h] and then to start a PARP inhibitor."
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
"Importantly, these new studies elucidate the molecular dynamics of these interactions, measure the kinetic and stoichiometric impact of mutations on protein binding and on the enzymatic activity of BAP1, and provide novel insights about the structural and dynamic parameters of the BAP1-ASXL2 interaction into single cell datasets that can inform future small-molecule approaches designed to reactivate latent wild-type UCH activity in BAP1 -mutant malignancies."
sparser
"Because most ASXL2 mutations are out-of-frame frameshift mutations in exons 11 and 12, at least in AML with t (18;21) [ xref ], the BAP1 binding region in ASXL2 is also unaffected, although it remains to be determined whether truncated ASXL2-BAP1 complexes exhibit enhanced DUB activity."
sparser
"Importantly, these new studies elucidate the molecular dynamics of these interactions, measure the kinetic and stoichiometric impact of mutations on protein binding and on the enzymatic activity of BAP1, and provide novel insights about the structural and dynamic parameters of the BAP1-ASXL2 interaction into single cell datasets that can inform future small-molecule approaches designed to reactivate latent wild-type UCH activity in BAP1 -mutant malignancies."
sparser
"Because most ASXL2 mutations are out-of-frame frameshift mutations in exons 11 and 12, at least in AML with t (18;21) [ xref ], the BAP1 binding region in ASXL2 is also unaffected, although it remains to be determined whether truncated ASXL2-BAP1 complexes exhibit enhanced DUB activity."
reach
"Functional studies reveal that BAP1 decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression in a deubiquitinating dependent manner, and that BAP1 inhibits cystine uptake by repressing SLC7A11 expression, leading to elevated lipid peroxidation and ferroptosis."
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
"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 ."
reach
"Functional studies reveal that BAP1 decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression in a deubiquitinating dependent manner, and that BAP1 inhibits cystine uptake by repressing SLC7A11 expression, leading to elevated lipid peroxidation and ferroptosis."
sparser
"Gerlinger and
colleagues have shown that intragenic VHL mutations and loss of 3p
are the only uniformly truncal events in ccRCC.( xref ) We have shown that loss of PBRM1 and BAP1 are mutually exclusive and
that loss of PBRM1 is associated with better outcomes than loss of BAP1.( xref , xref , xref ) Herein we validate previous results
from a meta-analysis showing that PBRM1 and SETD2 mutations cooperate in ccRCC.( xref )
Specifically, we find that H3K36me3 loss is 3 times more likely in PBRM1-negative
tumors than in those that express PBRM1."
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
"We previously evaluated
the prognostic impact of BAP1 and PBRM1 to define epigenetic subtypes of clear
cell renal cell carcinoma.( xref , xref ) To examine the association of H3K36me3
with BAP1 and PBRM1 protein expression, we evaluated the expression of all 3
markers dichotomized as positive versus negative in clear cell renal cell
carcinoma samples with available staining ( xref )."
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
sparser
"Gerlinger and
colleagues have shown that intragenic VHL mutations and loss of 3p
are the only uniformly truncal events in ccRCC.( xref ) We have shown that loss of PBRM1 and BAP1 are mutually exclusive and
that loss of PBRM1 is associated with better outcomes than loss of BAP1.( xref , xref , xref ) Herein we validate previous results
from a meta-analysis showing that PBRM1 and SETD2 mutations cooperate in ccRCC.( xref )
Specifically, we find that H3K36me3 loss is 3 times more likely in PBRM1-negative
tumors than in those that express PBRM1."
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
"We previously evaluated
the prognostic impact of BAP1 and PBRM1 to define epigenetic subtypes of clear
cell renal cell carcinoma.( xref , xref ) To examine the association of H3K36me3
with BAP1 and PBRM1 protein expression, we evaluated the expression of all 3
markers dichotomized as positive versus negative in clear cell renal cell
carcinoma samples with available staining ( xref )."
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
reach
"Genetic markers of ccRCC include biallelic inactivation of Von Hippel-Lindau (VHL) tumor suppressor genes; negative regulators of hypoxia inducible factor (HIF) protein; copy number changes of chromosome 3p, 5q, and 14q genes; and chromatin modifying enzyme high mutation frequencies, such as protein polybromo-1 (PBRM1), SET domain containing 2 (SETD2), and BRCA1 associated protein-1 (BAP1) [XREF_BIBR]."
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
"This raises the possibility for genetic cooperation with BAP1-driven pathogenicity in tumor B, but this particular mutation has not been previously noted to be pathogenic.At present, more than 7 years post- resection, Patient A has no clinical or radiographic evidence of newly recurrent or progressive disease."
reach
"The findings are in accordance with previous reports that reduced expression or inactivation of BAP1 in tumors, which often results from germline-inactivating or somatic-inactivating BAP1 mutations or deletions, increases tumor susceptibility, or predicts worse clinical outcomes ."
reach
"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)."
IHC affects BAP1
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IHC increases the amount of BAP1.
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reach
"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."
reach
"We previously demonstrated that BAP1 and PBRM1 expression by immunohistochemistry (IHC) are highly correlated with mutation status (P = 3E-58 and 4E-23 respectively 34 and that BAP1 and PBRM1 expression by IHC are independent predictors of both disease-free survival and overall survival in the localized disease setting."
reach
"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."
IHC inhibits BAP1.
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IHC decreases the amount of BAP1.
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reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR Given that real rate of germline BAP1 mutations is likely to be less than 1%, it is reasonable that formal genetic testing for BAP1 mutation be reserved for those patients who are considered high-risk based on family and personal history and demonstrate loss of BAP1 expression by IHC."
reach
"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 activates BAP1.
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"BRCA1-associated protein 1 (BAP1) deubiquitinase antagonizes the ubiquitin-mediated activation of FoxK2 target genes. Okino Y(1), Machida Y(1), Frankland-Searby S(2), Machida YJ(3). Author information: (1)From the Departments of Oncology and. (2)Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905. (3)From the Departments of Oncology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905 machida.yuichi@mayo.edu. BRCA1-associated protein 1 (BAP1), which is frequently mutated in cancer, functions as a deubiquitinase (DUB) for histone H2A.BAP1 represses FoxK2 target genes, and this effect requires BAP1 DUB activity but not interaction with HCF-1"
BAP1 affects Neoplasm Metastasis
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BAP1 activates Neoplasm Metastasis.
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BAP1 activates Neoplasm Metastasis. 10 / 17
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Mutated BAP1 activates Neoplasm Metastasis. 3 / 3
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BAP1 inhibits Neoplasm Metastasis.
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BAP1 inhibits Neoplasm Metastasis. 10 / 15
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reach
"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 affects apoptotic process
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BAP1 activates apoptotic process.
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BAP1 inhibits apoptotic process.
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BAP1 inhibits apoptotic process. 5 / 5
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"For instance, while loss of Bap1 activates intrinsic apoptosis in several mouse cell types (hepatocytes, keratinocytes, fibroblasts, and embryonic stem cells) in an RNF2 dependent fashion, the Bap1 loss enhances proliferation of melanocytes in association with upregulation of lineage specific oncogenes MITF and BCL2, independently of RNF2."
reach
"Since both BAP1 and PTEN inhibit apoptosis in a similar way, increasing the likelihood for pre-malignant cells to survive, it is tempting to speculate that also PTEN mutations may contribute to mesothelioma development in carriers of PTEN mutations, as demonstrated in animal models carrying germline BAP1 mutations with even minimal exposure to asbestos [30]."
reach
"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 cell death
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BAP1 activates cell death.
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BAP1 activates cell death. 10 / 23
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reach
"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. 9 / 9
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reach
"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]."
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."
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."
sparser
"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 )."
sparser
"Homology of the BAP1-UCH and other UCH-like proteins infers that this BAP1 motif functions in either ubiquitin-mediated, proteasomal degradation or some other ubiquitin-facilitated regulatory pathways that are involved in BRCA1 function, cellular proliferation, differentiation, and/or homeostatic processes ( xref , xref , 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
"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 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
"By comparing tumours which cluster with the cell lines based on CNAs with tumours that cluster away from the cell lines, we found that the tumours likely to be best represented by the cell lines carry hallmarks of aggressive disease, such as higher stage, higher grade, greater extent of CNAs, and more frequent mutations in genes such as SETD2, BAP1 and MTOR , which have been associated with more aggressive disease and poorer outcomes."
sparser
"These tumours also display a higher extent of copy number aberrations (mean fraction genome altered: 19% versus 12%), and more frequent mutations in genes such as BAP1 (12.3% versus 5.4%), SETD2 (12.7% versus 8.1%) and MTOR (6% versus 4.7%), which are associated with more aggressive disease (though only BAP1 has a statistically significant difference— P value 0.025, Fisher's exact test)."
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
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)."
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
"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 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
"By comparing tumours which cluster with the cell lines based on CNAs with tumours that cluster away from the cell lines, we found that the tumours likely to be best represented by the cell lines carry hallmarks of aggressive disease, such as higher stage, higher grade, greater extent of CNAs, and more frequent mutations in genes such as SETD2, BAP1 and MTOR , which have been associated with more aggressive disease and poorer outcomes."
sparser
"These tumours also display a higher extent of copy number aberrations (mean fraction genome altered: 19% versus 12%), and more frequent mutations in genes such as BAP1 (12.3% versus 5.4%), SETD2 (12.7% versus 8.1%) and MTOR (6% versus 4.7%), which are associated with more aggressive disease (though only BAP1 has a statistically significant difference— P value 0.025, Fisher's exact test)."
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
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 Neoplasm Invasiveness
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BAP1 inhibits Neoplasm Invasiveness.
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3
12
BAP1 inhibits Neoplasm Invasiveness. 10 / 15
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3
12
reach
"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)."
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."
BAP1 activates Neoplasm Invasiveness.
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9
BAP1 activates Neoplasm Invasiveness. 8 / 8
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8
Mutated BAP1 activates Neoplasm Invasiveness. 1 / 1
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1
BAP1 affects Multiple Myeloma
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18
5
BAP1 activates Multiple Myeloma.
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11
BAP1 activates Multiple Myeloma. 7 / 7
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7
reach
"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 Multiple Myeloma. 4 / 4
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4
BAP1 inhibits Multiple Myeloma.
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7
BAP1 binds Multiple Myeloma.
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5
BAP1 binds Multiple Myeloma. 5 / 5
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5
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 cell differentiation
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22
BAP1 activates cell differentiation.
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12
BAP1 activates cell differentiation. 10 / 10
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10
BAP1 bound to ASXL1-MT activates cell differentiation. 2 / 2
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2
BAP1 inhibits cell differentiation.
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10
BAP1 inhibits cell differentiation. 8 / 8
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8
BAP1 bound to ASXL1-MT inhibits cell differentiation. 2 / 2
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2
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
"Instead, overexpression of the Myc tagged truncated BAP1 L-mutant [Myc-BAP1 (L)] (the L family mutant BAP1 which lacks the N-terminus domain 5) showed an almost complete loss of interaction with IP3R3 compared to Myc tagged WT BAP1 (Myc-BAP1) (XREF_FIG), while catalytic inactive BAP1 (C91S) XREF_BIBR, XREF_BIBR did bind IP3R3 (XREF_FIG)."
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
"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
"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."
reach
"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."
BAP1 inhibits BAP1.
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4
BAP1 activates BAP1.
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6
reach
"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 increases the amount of BAP1.
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5
BAP1 decreases the amount of BAP1.
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2
reach
"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."
sparser
"We have demonstrated that ASXL, via its AB box, acts as a molecular scaffold to recruit the BAP1-ULD domain to transcription factors that bind to specific target genes; the BAP1-UCH catalytic domain then removes ubiquitin from histones on chromatin to regulate the expression of these transcriptional targets ( 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 )."
BAP1 affects cell growth
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17
BAP1 inhibits cell growth.
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14
BAP1 inhibits cell growth. 10 / 16
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14
reach
"BAP1 knockdown in vitro has resulted in decreased cell proliferation and mediation of apoptosis in MSTO211H, HMeso, and H2373 mesothelioma cell lines, and reintroduction of wild-type BAP1 in BAP1-null cell line NCI-H226 promoted cell growth, yet another study reported that this was counterbalanced by increased apoptosis, indicating that the consequences of in vitro manipulation may be cell type dependent [XREF_BIBR, XREF_BIBR]."
BAP1 activates cell growth.
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3
sparser
"We have demonstrated that ASXL, via its AB box, acts as a molecular scaffold to recruit the BAP1-ULD domain to transcription factors that bind to specific target genes; the BAP1-UCH catalytic domain then removes ubiquitin from histones on chromatin to regulate the expression of these transcriptional targets ( 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 )."
BAP1 affects ASXL1-MT
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18
BAP1 binds ASXL1-MT.
|
13
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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3
BAP1 activates ASXL1-MT.
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2
BAP1 affects transcription, DNA-templated
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4
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1
BAP1 activates transcription, DNA-templated.
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1
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1
BAP1 activates transcription, DNA-templated. 10 / 12
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1
10
1
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
"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
"RNA sequencing and chromatin immunoprecipitation coupled with quantitative PCR analyses revealed that reduced BAP1 expression suppressed upregulation of the transcription factors AP-1 and EGR1/2, as well as myeloid dysplasia associated genes, by retarding H2AK119Ub removal caused by ASXL1 mutation."
BAP1 inhibits transcription, DNA-templated.
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3
1
reach
"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 BAP1 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, OGT and PCG1-α, preventing them from proteasomal degradation."
ASXL1-MT affects BAP1
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15
ASXL1-MT binds BAP1.
|
13
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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2
BAP1 affects cell cycle
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2
12
BAP1 activates cell cycle.
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8
BAP1 inhibits cell cycle.
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2
4
BAP1 inhibits cell cycle. 6 / 6
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2
4
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."
reach
"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."
BAP1 affects H2Aub
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1
13
BAP1 inhibits H2Aub.
|
1
4
reach
"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.
|
4
reach
"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) ."
BAP1 deubiquitinates H2Aub.
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3
BAP1 increases the amount of H2Aub.
|
2
BAP1 affects 2'-O-methyluridine
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14
BAP1 inhibits 2'-O-methyluridine.
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7
BAP1 inhibits 2'-O-methyluridine. 7 / 7
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7
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)."
BAP1 activates 2'-O-methyluridine.
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7
MiR-31 affects BAP1
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13
MiR-31 decreases the amount of BAP1.
|
6
MiR-31 inhibits BAP1.
|
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
MiR-31 activates BAP1.
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2
BAP1 affects DNA repair
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4
9
BAP1 activates DNA repair. 10 / 13
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4
9
reach
"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."
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
"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
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
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 Mesothelioma
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11
BAP1 inhibits Mesothelioma.
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6
BAP1 activates Mesothelioma.
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5
BAP1 activates Mesothelioma. 5 / 5
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5
reach
"In this regard, mesothelioma is considered a malignancy that cannot be cured surgically; however, there are a few cases of patients from families with malignant mesothelioma caused by germline BAP1 or other tumor suppressor mutations who, because of screening and a high degree of suspicion, underwent surgery at a very early stage, and most of them are alive and apparently tumor-free 10 years postsurgical resection (2 of them at 18 years and 21 years, respectively, postsurgery)."
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 )."
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 )."
reach
"All three genes are located on chromosome 3p, as is VHL and as noted earlier, inactivation of both VHL and Bap1 in mice leads to both cystic and neoplastic lesions [86]; clearly, definition of the functional interactions between VHL, BAP1, PBRM1, and SET is a topic of urgent interest."
reach
"Instead, overexpression of the Myc tagged truncated BAP1 L-mutant [Myc-BAP1 (L)] (the L family mutant BAP1 which lacks the N-terminus domain 5) showed an almost complete loss of interaction with IP3R3 compared to Myc tagged WT BAP1 (Myc-BAP1) (XREF_FIG), while catalytic inactive BAP1 (C91S) XREF_BIBR, XREF_BIBR did bind IP3R3 (XREF_FIG)."
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 homologous recombination
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10
BAP1 activates homologous recombination.
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7
BAP1 activates homologous recombination. 5 / 5
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BAP1 activates homologous recombination. 2 / 2
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2
BAP1 inhibits homologous recombination.
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3
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 )."
reach
"All three genes are located on chromosome 3p, as is VHL and as noted earlier, inactivation of both VHL and Bap1 in mice leads to both cystic and neoplastic lesions [86]; clearly, definition of the functional interactions between VHL, BAP1, PBRM1, and SET is a topic of urgent interest."
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)."
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 Survival
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1
7
BAP1 inhibits Cell Survival.
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1
3
BAP1 activates Cell Survival.
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4
BAP1 affects Carcinogenesis
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10
BAP1 activates Carcinogenesis.
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8
BAP1 activates Carcinogenesis. 5 / 5
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5
reach
"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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3
BAP1 inhibits Carcinogenesis.
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2
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
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 ferroptosis
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2
7
BAP1 activates ferroptosis.
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2
4
BAP1 inhibits ferroptosis.
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3
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
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."
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 )."
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
"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 necrotic cell death
|
6
BAP1 affects miR-31
|
8
BAP1 inhibits miR-31.
|
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.
|
3
BAP1 binds miR-31.
|
2
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."
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 H2AK119ub1
|
1
7
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
"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 metabolic process
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7
BAP1 inhibits metabolic process.
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4
BAP1 inhibits metabolic process. 4 / 4
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4
reach
"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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3
BAP1 affects cell migration
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1
6
BAP1 inhibits cell migration.
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1
3
BAP1 activates cell migration.
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3
BAP1 affects calcium(2+)
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7
BAP1 increases the amount of calcium(2+).
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4
BAP1 activates calcium(2+).
|
3
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 DNA Damage
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7
BAP1 activates DNA Damage. 6 / 6
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6
Mutated BAP1 activates DNA Damage. 1 / 1
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1
reach
"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."
BAP1 affects ASXL
|
7
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."
N1ICD affects BAP1
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6
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 cell adhesion
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6
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."
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."
BAP1 affects PRC2_complex
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3
3
BAP1 binds PRC2_complex.
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1
3
BAP1 inhibits PRC2_complex.
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2
BAP1 affects N1ICD
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6
BAP1 affects Histone_H2A
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6
BAP1 ubiquitinates Histone_H2A.
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3
BAP1 ubiquitinates Histone_H2A. 3 / 3
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3
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]."
BAP1 deubiquitinates Histone_H2A.
|
3
BAP1 deubiquitinates Histone_H2A. 3 / 3
|
3
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]."
BAP1 affects E3_Ub_ligase
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2
4
BAP1 inhibits E3_Ub_ligase.
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2
1
BAP1 binds E3_Ub_ligase.
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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."
|
2
4
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
"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
"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."
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."
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
"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
"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
"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."
Multiple Myeloma affects BAP1
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5
BAP1 binds Multiple Myeloma. 5 / 5
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5
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 ."
GEP affects BAP1
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5
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 ."
|
2
3
sparser
"Alternatively, UBE2O, which has been reported to suppress its function by recruiting BAP1 to the cytosol, xref is mutated in ESCC and in other esophageal carcinomas (see COSMIC data base). xref It is possible that altered UBE2O behaves as an oncoprotein like activated EGFR or RAS family proteins."
BAP1 affects mutations
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5
BAP1 affects double-strand break repair
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5
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 )."
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."
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
"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
"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."
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 H3K27me3
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5
BAP1 affects GEP
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5
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 ."
ASXL proteins affects BAP1
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5
3p21.1 losses affects BAP1
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5
RING finger domain affects BAP1
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4
PRC2_complex affects BAP1
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1
3
MP65 affects BAP1
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4
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 radioresistance
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4
BAP1 affects glycolytic process
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4
BAP1 inhibits glycolytic process.
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2
BAP1 inhibits glycolytic process. 2 / 2
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2
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)."
BAP1 activates glycolytic process.
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2
BAP1 affects gemcitabine
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4
BAP1 affects angiogenesis
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1
3
BAP1 affects RING finger domain
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4
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 MP65
|
4
BAP1 affects H2AK119ub
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4
BAP1 affects DEUBAD
|
4
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 ASXL1/2
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3
1
ASXL1/2 affects BAP1
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3
1
Ubiquitin-conjugating enzyme affects BAP1
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3
Ubiquitin-conjugating enzyme ubiquitinates BAP1.
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2
Ubiquitin-conjugating enzyme activates BAP1.
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1
Ubiquitin-conjugating enzyme activates BAP1. 1 / 1
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1
Transcriptional regulator affects BAP1
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3
Glycolic acid affects BAP1
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3
Glycolic acid inhibits BAP1.
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2
Glycolic acid binds BAP1.
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1
Glycolic acid binds BAP1. 1 / 1
|
1
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."
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."
NCIT:C94600 affects BAP1
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3
HDAC inhibitors affects BAP1
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3
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."
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."
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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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."
BAP1 affects transcriptional regulator
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3
BAP1 affects localization
|
3
BAP1 affects laminin
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3
BAP1 affects biosynthetic process
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3
BAP1 activates biosynthetic process. 2 / 2
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Mutated BAP1 activates biosynthetic process. 1 / 1
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1
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 ."
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)."
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)."
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."
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."
BAP1 affects COPI complex
|
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
BAP1 affects BARD1, and E3_Ub_ligase
|
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."
BAP1 affects ASXL proteins
|
3
Hsa-miR-200c-3p affects BAP1
2
|
Hsa-miR-200b-3p affects BAP1
2
|
Hsa-miR-200a-3p affects BAP1
2
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Hsa-miR-141-3p affects BAP1
2
|
Class 2 affects GEP
|
2
Bisphenol A affects BAP1
2
|
Betulinic acid affects BAP1
|
2
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
"By comparing tumours which cluster with the cell lines based on CNAs with tumours that cluster away from the cell lines, we found that the tumours likely to be best represented by the cell lines carry hallmarks of aggressive disease, such as higher stage, higher grade, greater extent of CNAs, and more frequent mutations in genes such as SETD2, BAP1 and MTOR , which have been associated with more aggressive disease and poorer outcomes."
sparser
"These tumours also display a higher extent of copy number aberrations (mean fraction genome altered: 19% versus 12%), and more frequent mutations in genes such as BAP1 (12.3% versus 5.4%), SETD2 (12.7% versus 8.1%) and MTOR (6% versus 4.7%), which are associated with more aggressive disease (though only BAP1 has a statistically significant difference— P value 0.025, Fisher's exact test)."
RA-9 affects BAP1
|
2
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
"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."
PBRM1 affects H3K36me3
|
2
sparser
"We previously evaluated
the prognostic impact of BAP1 and PBRM1 to define epigenetic subtypes of clear
cell renal cell carcinoma.( xref , xref ) To examine the association of H3K36me3
with BAP1 and PBRM1 protein expression, we evaluated the expression of all 3
markers dichotomized as positive versus negative in clear cell renal cell
carcinoma samples with available staining ( xref )."
NP_828865 affects BAP1
2
|
NEAT-1 affects BAP1
|
2
sparser
"By comparing tumours which cluster with the cell lines based on CNAs with tumours that cluster away from the cell lines, we found that the tumours likely to be best represented by the cell lines carry hallmarks of aggressive disease, such as higher stage, higher grade, greater extent of CNAs, and more frequent mutations in genes such as SETD2, BAP1 and MTOR , which have been associated with more aggressive disease and poorer outcomes."
sparser
"These tumours also display a higher extent of copy number aberrations (mean fraction genome altered: 19% versus 12%), and more frequent mutations in genes such as BAP1 (12.3% versus 5.4%), SETD2 (12.7% versus 8.1%) and MTOR (6% versus 4.7%), which are associated with more aggressive disease (though only BAP1 has a statistically significant difference— P value 0.025, Fisher's exact test)."
H3K36me3 affects PBRM1
|
2
sparser
"We previously evaluated
the prognostic impact of BAP1 and PBRM1 to define epigenetic subtypes of clear
cell renal cell carcinoma.( xref , xref ) To examine the association of H3K36me3
with BAP1 and PBRM1 protein expression, we evaluated the expression of all 3
markers dichotomized as positive versus negative in clear cell renal cell
carcinoma samples with available staining ( xref )."
GEP affects class 2
|
2
CRISPR affects BAP1
|
2
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."
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 vorinostat
|
2
BAP1 affects viability migration ECA109 cells
|
2
BAP1 affects ubiquitination
|
1
BAP1 affects mitochondrial protein
|
2
BAP1 affects mastoparan-M
|
2
BAP1 affects inflammatory response
|
2
BAP1 affects homeostatic process
|
2
BAP1 activates homeostatic process. 2 / 2
|
2
BAP1 affects growth
|
1
BAP1 affects gene expression
|
2
BAP1 affects endoplasmic reticulum
|
1
1
BAP1 binds endoplasmic reticulum.
|
1
Endoplasmic reticulum binds BAP1. 1 / 1
|
1
BAP1 activates endoplasmic reticulum.
|
1
Mutated BAP1 activates endoplasmic reticulum. 1 / 1
|
1
BAP1 affects dedifferentiation
|
2
BAP1 affects class 2
|
2
BAP1 affects cellular metabolic process
|
2
eidos
"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 ."
BAP1 affects betulinic acid
|
2
BAP1 affects assembly constitutive BRCA1 foci
|
2
eidos
"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 affects activity
|
2
BAP1 affects TRAIL receptors
|
2
BAP1 affects Polycomb
|
1
1
BAP1 affects Pancreatitis
|
2
BAP1 activates Pancreatitis. 2 / 2
|
2
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."
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
"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."
BAP1 affects NP_828865
2
|
BAP1 affects Mitochondrial Proteins
|
2
sparser
"By comparing tumours which cluster with the cell lines based on CNAs with tumours that cluster away from the cell lines, we found that the tumours likely to be best represented by the cell lines carry hallmarks of aggressive disease, such as higher stage, higher grade, greater extent of CNAs, and more frequent mutations in genes such as SETD2, BAP1 and MTOR , which have been associated with more aggressive disease and poorer outcomes."
sparser
"These tumours also display a higher extent of copy number aberrations (mean fraction genome altered: 19% versus 12%), and more frequent mutations in genes such as BAP1 (12.3% versus 5.4%), SETD2 (12.7% versus 8.1%) and MTOR (6% versus 4.7%), which are associated with more aggressive disease (though only BAP1 has a statistically significant difference— P value 0.025, Fisher's exact test)."
BAP1 affects Interferon
|
1
1
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."
BAP1 affects Histone_H3
|
2
BAP1 leads to the methylation of Histone_H3 at position 27. 1 / 1
|
1
BAP1 leads to the methylation of Histone_H3 on lysine. 1 / 1
|
1
BAP1 affects Histone_H2B
|
2
BAP1 deubiquitinates Histone_H2B. 2 / 2
|
2
reach
"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
|
2
sparser
"We previously evaluated
the prognostic impact of BAP1 and PBRM1 to define epigenetic subtypes of clear
cell renal cell carcinoma.( xref , xref ) To examine the association of H3K36me3
with BAP1 and PBRM1 protein expression, we evaluated the expression of all 3
markers dichotomized as positive versus negative in clear cell renal cell
carcinoma samples with available staining ( xref )."
BAP1 affects H2AK119Ub
|
2
BAP1 affects Genomic Instability
|
2
BAP1 affects GEP, and class 2
|
2
BAP1 affects EP4 receptor
|
2
BAP1 affects DNA replication
|
2
BAP1 affects DNA break repair
|
2
BAP1 affects Chromosomal Instability
|
1
1
BAP1 affects ASXH domain
|
2
BAP1 affects 6-dEB
|
2
ASXL1 affects ASXH domain
|
2
AM146 affects BAP1
|
2
2'-O-methyluridine affects BAP1
|
2
2'-O-methyluridine inhibits BAP1. 2 / 2
|
2
reach
"The peculiar UM proneness in MBD4-mutant carriers (13 out of 23 carriers; XREF_TABLE) remains unexplained, but the fact that the frequent M3 in UM inactivates wild-type copies of both BAP1 and MBD4 suppressor genes may at least in part explain the frequent inactivation of MBD4 in UM."
Tumour suppressor affects BAP1
|
1
BAP1 binds tumour suppressor. 1 / 1
|
1
SiPDHK1 affects BAP1
|
1
Recombinational repair affects BAP1
|
1
Recombinational repair binds BAP1. 1 / 1
|
1
reach
"Major components of the V. cholerae biofilm are Vibrio polysaccharide (VPS), which is produced by proteins encoded in the vps-I and vps-II gene clusters, as well as matrix proteins (RbmA, RbmC, and Bap1) that facilitate cell-cell and cell-surface interactions and contribute to biofilm architecture [XREF_BIBR - XREF_BIBR]."
Monomethylarsonous acid affects BAP1
1
|
Hsa-miR-4489 affects BAP1
1
|
Hsa-miR-4283 affects BAP1
1
|
Hsa-miR-1229-3p affects BAP1
1
|
Folic acid affects BAP1
1
|
Extrascleral extension affects BAP1
|
1
Endoplasmic reticulum affects BAP1
|
1
Endoplasmic reticulum binds BAP1. 1 / 1
|
1
Cyclosporin A affects BAP1
1
|
Alpha-D-galactose affects BAP1
|
1
Alpha-D-galactose binds BAP1. 1 / 1
|
1
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
sparser
"TNK2 is known to encourage prostate tumorigenesis, xref – xref Some of the down-regulated genes, like SEMA3F , BAK1 , and BAP1 are associated with tumor suppression. xref , xref – xref Many of the down-regulated genes are also associated with decreased invasion and motility, such as DDR1 , ZYX , NES , and PLEC . xref – xref "
RP23-49C8.1 affects BAP1
1
|
RNA, Small Interfering affects BAP1
|
1
RNA, Small Interfering inhibits BAP1. 1 / 1
|
1
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
OCM affects CM
|
1
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
H2AK119 affects BAP1
|
1
Gon4l/Udu affects BAP1
|
1
E2/E3 affects BAP1
|
1
DUB inhibitor affects BAP1
|
1
reach
"b-AP15 is not an indiscriminate DUB inhibitor, since in isolated DUB assays it does not inhibit USP2/7/8, UCHL1, UCHL3 or BAP1 at 50 μM. Even though 19S inhibitory potency was modest, the Linder group showed that 37 inhibited tumour progression in four different in vivo solid tumour models in mice (2.5-5 mg/kg by subcutaneous injection), validating the 19S regulatory particle as a new anticancer drug target."
CM affects OCM
|
1
BAP1 affects tumour suppressor
|
1
BAP1 binds tumour suppressor. 1 / 1
|
1
BAP1 affects tumor development
|
1
reach
"This screen, along with subsequent validation experiments, identifies a compendium of genes whose silencing causes tamoxifen resistance (including BAP1, CLPP, GPRC5D, NAE1, NF1, NIPBL, NSD1, RAD21, RARG, SMC3, and UBA3) and also a set of genes whose silencing causes sensitivity to this endocrine agent (C10orf72, C15orf55 and NUT, EDF1, ING5, KRAS, NOC3L, PPP1R15B, RRAS2, TMPRSS2, and TPM4)."
BAP1 affects sites
|
1
BAP1 affects sensitivity radiation
|
1
BAP1 affects reprogramming cell metabolism
|
1
BAP1 affects replication fork
|
1
BAP1 activates replication fork. 1 / 1
|
1
eidos
"We previously reported that the stability of Ino80 , the catalytic ATPase subunit of INO80 , is regulated by the ubiquitin proteasome system and that BRCA1-associated protein-1 ( BAP1 ) , a nuclear deubiquitinase with tumor suppressor activity , stabilizes Ino80 via deubiquitination and promotes replication fork progression ."
BAP1 affects recombinational repair
|
1
Recombinational repair binds BAP1. 1 / 1
|
1
reach
"Major components of the V. cholerae biofilm are Vibrio polysaccharide (VPS), which is produced by proteins encoded in the vps-I and vps-II gene clusters, as well as matrix proteins (RbmA, RbmC, and Bap1) that facilitate cell-cell and cell-surface interactions and contribute to biofilm architecture [XREF_BIBR - XREF_BIBR]."
BAP1 affects phosphorylation ERK1 JNK
|
1
BAP1 affects phenotypical evolution WDPM
|
1
BAP1 affects pathogenesis human cancers
|
1
BAP1 affects nuclear export134
|
1
BAP1 affects multinucleation
|
1
BAP1 affects mesenchymal-epithelial transition kidney tumor cells
|
1
BAP1 affects interaction
|
1
BAP1 affects glycolic acid
|
1
Glycolic acid binds BAP1. 1 / 1
|
1
BAP1 affects glucose deprivation-induced apoptosis
|
1
BAP1 affects deubiquitylase adaptor module DEUBAD
|
1
BAP1 affects anaerobic glycolysis energy
|
1
BAP1 affects alpha-D-galactose
|
1
Alpha-D-galactose binds BAP1. 1 / 1
|
1
BAP1 affects activation cysteine-dependent cell death
|
1
reach
"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."
BAP1 affects UM metastasis
|
1
BAP1 affects Small Cell Lung Carcinoma
|
1
BAP1 activates Small Cell Lung Carcinoma. 1 / 1
|
1
sparser
"TNK2 is known to encourage prostate tumorigenesis, xref – xref Some of the down-regulated genes, like SEMA3F , BAK1 , and BAP1 are associated with tumor suppression. xref , xref – xref Many of the down-regulated genes are also associated with decreased invasion and motility, such as DDR1 , ZYX , NES , and PLEC . xref – xref "
BAP1 affects S phase OCM1 cells NCI-H226 lung carcinoma cell line
|
1
BAP1 affects RP23-49C8.1
1
|
BAP1 affects NRPSs
|
1
sparser
"Several recent studies have shown that, in cc RCC, in addition to inactivating mutations in VHL tumor suppressor genes, genes such as BAP1, PBRM1, SETD2, and KDM5C play a role in tumor development, for example, causing mutations in the ubiquitin-mediated protein hydrolysis pathway (UMPP) in cc RCC; recent sequencing studies of cc RCC sequencing studies have recently identified chromatin modification genes such as PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2, and BAP1 that are highly associated with inactivating point mutations in their progression and poor prognosis."
BAP1 affects KLF5-mediated growth melanoma
|
1
BAP1 affects KIRC
|
1
BAP1 affects ISGF3
|
1
BAP1 affects HOXA gene
|
1
BAP1 affects H2AK119
|
1
BAP1 affects Gon4l/Udu
|
1
BAP1 affects DSB repair
|
1
BAP1 affects Carcinoma, Squamous Cell
|
1
Mutated BAP1 activates Carcinoma, Squamous Cell. 1 / 1
|
1
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."
sparser
"TNK2 is known to encourage prostate tumorigenesis, xref – xref Some of the down-regulated genes, like SEMA3F , BAK1 , and BAP1 are associated with tumor suppression. xref , xref – xref Many of the down-regulated genes are also associated with decreased invasion and motility, such as DDR1 , ZYX , NES , and PLEC . xref – xref "
BAP1 affects 6dEB
|
1
sparser
"TNK2 is known to encourage prostate tumorigenesis, xref – xref Some of the down-regulated genes, like SEMA3F , BAK1 , and BAP1 are associated with tumor suppression. xref , xref – xref Many of the down-regulated genes are also associated with decreased invasion and motility, such as DDR1 , ZYX , NES , and PLEC . xref – xref "
ASXL2-AB box affects BAP1
|
1
1
|
1,4-dithiothreitol affects BAP1
|
1
1,4-dithiothreitol inhibits BAP1. 1 / 1
|
1
(S)-nicotine affects BAP1
1
|