IndraLab

"HCF-1 is modified with ubiquitin in vivo, and ectopic studies suggest BAP1 deubiquitinates HCF-1."

"It has been proposed that BAP1 may modulate cell proliferation by deubiquitylating the transcriptional regulator HCF1."

"BAP1 also interacts with and deubiquitinates the transcriptional regulator host cell factor 1 (HCF1)."

"The massive increase of BAP1 expression with tumor cell proliferation was expected, as BAP1 regulates cell proliferation via deubiquitination of its target protein host cell factor-1 (HCF1), which plays a critical role at multiple stages of the cell cycle [55, 56]."

"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."

"It has been proposed that ubiquitylation of HCF1 blocks E2F responsive promoter activity, and that HCF1 deubiquitylation by BAP1 would remove this inhibition and promote cell proliferation 33."

"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 deubiquitinates poly-ubiquitinated HCF-1, yet depletion of BAP1 has shown mixed effects on the stability of HCF-1 protein levels [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."

"Additionally, BAP1 deubiquitinates the lysine residues of HCF-1 to recruit multiprotein complex partners (i.e. OGT and PGC1α) and stabilize these partners, thereby potentiating transcriptional regulatory effects (49)."

"Compared with GST and BAP1-C91S, BAP1 specifically decreased KLF5 polyubiquitination (XREF_FIG; XREF_SUPPLEMENTARY)."

"BAP1 interacts directly with KLF5 and stabilizes KLF5 via deubiquitination."

"In breast cancer cell lines, BAP1 plays an oncogenic function by directly deubiquitinating and stabilizing KLF5 (Kruppel-like factor 5)."

"BAP1, but not BAP1-C91S, markedly decreased KLF5 protein polyubiquitination (XREF_FIG, lanes 3 and 4), whereas another DUB, A20, did not decrease KLF5 polyubiquitination (XREF_FIG, lane 5)."

"Second, BAP1 decreases KLF5 polyubiquitination and increases KLF5 protein stability in a DUB activity dependent manner."

"BAP1 antagonizes WWP1 mediated transcription factor KLF5 ubiquitination and inhibits autophagy to promote melanoma progression."

"Finally, we demonstrated that knockdown of endogenous BAP1 increased the ubiquitination of endogenous KLF5 in HCC1806 (XREF_FIG)."

"In line with this notion, BAP1 depletion resulted in reduced localization of RPA, RAD51 and BRCA1 to IRIF or microlaser irradiation site [100,101], although it remains ambiguous whether either histone[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"In addition to MCRS1, a recent study revealed that BAP1 deubiquitinates and stabilizes Ino80, a key subunit of the INO80 chromatin remodeling complex implicated in DNA replication during stress."

"BAP1 overexpression also abolished basal Ino80 ubiquitination (XREF_FIG and XREF_FIG, rightmost lanes)."

"BAP1 interacts with and deubiquitylates INO80, playing a critical role in stabilizing and targeting the INO80 chromatin remodeling complex to the replication forks."

"Since BAP1 deubiquitinates and stabilizes Ino80, we investigated the relationship between CHIP and BAP1 in Ino80 ubiquitination."

"BAP1 deubiquitylates INO80 and thereby protects the protein from ubiquitin mediated proteolysis."

"A recent study has linked the deubiquitination of gamma-tubulin by BAP1 to breast cancer."

"While the mechanism remains to be fully elucidated, it seems that deubiquitylation of gamma-tubulin by BAP1 during mitosis allows proper spindle organisation and function [XREF_BIBR]."

"Another study showed de-ubiquitination of gamma-tubulin by BAP1 prevents chromosome instability in breast cancer cells [15]."

"Deubiquitination of gamma-tubulin by BAP1 prevents chromosome instability in breast cancer cells."

"We hypothesized that BAP1 might deubiquitylate and stabilize IP3R3."

"At the ER, BAP1-dependent deubiquitination of the type 3 inositol-1,4,5-trisphosphate receptor (IP3R3) is necessary to sustain the IP3R3 ER channel integrity (11,55)."

"Along with maintenance of IP3R3 ER channel integrity, BAP1-dependent deubiquitination of IP3R3 may change the threshold for IP3R3 activation by Ca itself or IP3."

"BAP1 (C91S), despite being able to bind IP3R3 (XREF_FIG), failed to deubiquitylate IP3R3 (NT) (XREF_FIG and XREF_FIG), underscoring the requirement of BAP1 catalytic activity."

"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."

"Further mechanistic studies demonstrated that BAP1 suppresses SLC7A11 expression partly by deubiquitinating histone 2A ubiquitination to promote ferroptosis."

"Recently, it has been found that BAP1 can inhibit the expression of SLC7A11 to suppress the uptake of cystine by deubiquitinating histone 2A on the SLC7A11 promoter."

"BRCA1 associated protein 1 (BAP1) is a ubiquitin C-terminal hydrolase that deubiquitinates histone H2AK119ub and other proteins and regulates the expression of multiple genes."

"As a possible mechanism of BRCA1 stabilization by BAP1 transduction in this study, we speculated that the ubiquitination of BRCA1 protein might be directly deubiquitinated by BAP1."

"We hypothesized that BAP1 might deubiquitinate BRCA1 and protect it from proteasome mediated degradation; this might explain the BRCA1 stabilization by the mutant BAP1 forms that retained the DUB activity."

"BAP1 also controls G1/S cell cycle progression by regulating BRCA-1 [111], Ying Yang 1 (YY-1), and host cell factor 1 (HCF-1)"

"3 Nuclear BAP1 indeed deubiquitylates BRCA1 associated RING domain 1 (BARD1), which in a heterodimer with BRCA1, forms the E3 ubiquitin ligase that regulates the DNA damage response (DDR)."

"XREF_BIBR, XREF_BIBR, XREF_BIBR BAP1 also deubiquitylates OGT and regulates its levels."

"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."

"Together, our study demonstrates that KEAP1 deubiquitination by BAP1 is novel tumor suppressive mechanism of LUAD."

"BAP1 Downregulates NRF2 Target Genes and Exerts Anti-Tumorigenic Effects by Deubiquitinating KEAP1 in Lung Adenocarcinoma."

"In the present study, we have identified that BAP1 deubiquitinates KEAP1 by binding to the BTB domain."

"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 2A in the regulatory chromatin of the of SLC7A11 gene, which encodes, a key transporter of extracellular cysteine."

"The mechanism may be that BAP1 represses the transcription of SLC7A11 by reducing histone 2A ubiquitination (H2Aub) on the SLC7A11 gene (49)."

"Other studies in mammalian cells have also shown that BAP1 represses the expression of some target genes with BAP1 dependent deubiquitination of H2Aub on the corresponding gene promoters XREF_BIBR, XREF_BIBR."

"In conclusion, we found that BAP1 can deubiquitinate H2Aub and induces radioresistance in HNSCC cells via modulation of HR."

"BAP1 deubiquitinates H2Aub."

"XREF_BIBR reported that BAP1 is phosphorylated at serine 592 following DNA damage, that phospho-BAP1 causes deubiquitination of H2AK119ub1, and that this signal promotes the HR pathway."

"87 As Drosophila Calypso, human BAP1 deubiquitylates H2AK119ub1."

"Mammalian BAP1 deubiquitylates H2AK119ub1, 87 and BAP1 reintroduction into BAP1 deficient ccRCC cell lines affected global levels of H2AK119ub1."

"BAP1 can physically bind to and deubiquitinate PTEN, which inhibits the ubiquitination mediated degradation of PTEN and thus stabilizes PTEN protein."

"However, another study suggests that BAP1 may deubiquitinate and stabilize PTEN, leading to Akt inhibition [133]."

"However, this is unlikely to account for the stabilization of PGC-1alpha by OGT because 1) the S333A mutation, which bypasses the effects of O GlcNAcylation on the proteasome, increases PGC-1alpha ubiquitination and decreases its stability, 2) HCF-1 and BAP1 have no effect on proteasome function or global ubiquitination (XREF_FIG and data not shown), but can decrease PGC-1alpha ubiquitination and increase its stability."

"Overexpression of BAP1 does not increase global ubiquitination, but substantially increases the level of PGC-1alpha and decreases PGC-1alpha ubiquitination as normalized to the protein level (XREF_FIG)."

"Since BAP1 is a de-ubiquitinating enzyme, we explored whether BAP1 de-ubiquitinates and stabilizes MCRS1."

"Moreover, de-ubiquitination of MCRS1 by BAP1 plays important roles in regulating proper mitotic progression and prevents chromosome instability.The yeast two-hybrid screen was performed with full leng[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

"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]."

"Subsequent WB using anti-HA and anti- Flag antibodies showed that the BAP1 WT, but not a MT, deubiquitinated H2B in vivo."

"It has been proposed that BAP1 may modulate cell proliferation by deubiquitylating the transcriptional regulator HCF1."

"Furthermore, BAP1 deubiquitylates the deubiquitylase adaptor module DEUBAD of ASXL2, leading to its stabilization."

"BAP1 also controls G1/S cell cycle progression by regulating BRCA-1 [111], Ying Yang 1 (YY-1), and host cell factor 1 (HCF-1)"

"The association between BAP1 and 14-3-3 protein releases the apoptotic inducer protein Bax from 14-3-3 and promotes cell death through the intrinsic apoptosis pathway."

"Deubiquitination of <U+00A6><c3>-tubulin by BAP1 prevents chromosome instability in breast cancer cells"

"Our findings reveal that BAP1 deubiquitinates LKB1, inhibits its degradation, and stabilises it, thereby affecting AMPK activation and downstream mTOR activity."

"Downstream of ASXN is the ASX homology (ASXH) domain (also known as the DEUBAD domain) encoded by exons 9-11, which participates in interactions with epigenetic regulatory proteins, including the BRCA1 Associated Protein 1 (BAP1) deubiquitinating protease [XREF_BIBR - XREF_BIBR]."

"The theoretical hypothesis is presented in XREF_FIG : Mutant Bap1 protein continues to deubiquitylate ubiquitous Notch signaling complexes, which are supposed to be degraded after ubiquitylation."

"Since K119 and K13/15 reside at distinct locations in the nucleosome (XREF_SUPPLEMENTARY) we asked whether BAP1 could also deubiquitinate K13/15."

"The calypso and BAP1 DUB deubiquitylates K119ub on histone H2A, leading to gene repression."

"BAP1 suppresses RCC cell proliferation and deubiquitinates H2Aub1 in renal cancer cells."

"Review"

"BAP1 deubiquitinates H2AK119Ub, regulating chromatin packing and gene expression (Scheuermann et al., 2010; Foglizzo et al., 2018)."

"28 ASXL1 may also collaborate with BAP1, loss of which led to a myelodysplastic syndrome like syndrome in a mouse model, to deubiquitinate H2AK119 at polycomb group targets."

"BRCA1 associated protein1 (BAP1) is a tumor suppressor involved in multiple cellular processes such as transcriptional regulation, chromatin modification by deubiquitinating histone 2A, and DNA repair"

"The tumour suppressor BRCA1-associated protein 1 (BAP1) encodes a nuclear deubiquitinating enzyme to reduce histone 2A ubiquitination (H2Aub) on chromatin."

"Review"

"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"

"A recent study indicated that BAP1 and its Drosophila homolog Calypso deubiquitinate H2AK119Ub, with minimal activity against H2BK120Ub or polyubiquitin chains (Scheuermann et al., 2010)."

"Mammalian BAP1 deubiquitylates H2AK119ub1, 87 and BAP1 reintroduction into BAP1 deficient ccRCC cell lines affected global levels of H2AK119ub1."

"Furthermore, BAP1 deubiquitylates the deubiquitylase adaptor module DEUBAD of ASXL2, leading to its stabilization."