IndraLab
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"Finally, it remains to be seen how the bidentate complex may affect deubiquitination of other PR-DUB substrates -- for instance BAP1 has been proposed to remove ubiquitin from its own C-terminal tail, as well as Host Cell Factor-1 (HCF-1; which binds within the BAP1 specific insert) and Ube2O XREF_BIBR, XREF_BIBR, XREF_BIBR, both of which are highly relevant to the role of the PR-DUB in cancers."
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"BAP1 is a 729 amino acid nuclear ubiquitin hydrolase that has been implicated in numerous cellular processes such as cell proliferation and DNA repair ( xref ) as well as chromatin-level control of gene expression ( xref ). xref For example, BAP1 has been shown to enhance progression through the G1-S checkpoint and subsequently induce cell death by a process with similarities to both apoptosis and necrosis. xref Additionally, BAP1 regulates cell proliferation by deubiquitinating host cell factor-1 (HCF-1), xref a chromatin-associated protein believed to activate and repress transcription by linking appropriate histone-modifying enzymes to a subset of transcription factors, in particular of the E2F family. xref BAP1 knockdown using small interfering RNA (siRNA) in MPM cell lines inhibited cell growth, and resulted in inactivation of HCF1 and downregulation of downstream E2F-responsive genes. xref It has also been shown that BAP1 and HCF-1 can form a ternary complex with the YY1 transcription factor to regulate gene expression. xref "
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"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
"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."
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"In 31 MPM tumors with wild-type BAP1, we sequenced the HCF1 kelch domain, which is required for BAP1 binding xref , xref , hypothesizing that HCF1 mutations that disrupt the BAP1-HCF1 interaction might substitute for BAP1 mutations in MPM tumorigenesis, but we found no mutations."
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" BAP1 has been suggested to be a tumour suppressor gene with a role in cell proliferation and growth inhibition. xref xref It has been suggested that the interaction of BAP1 with host cell factor-1 (HCF-1) is critical for its growth inhibition function. xref xref In addition to UM, somatic mutations in BAP1 have been identified in breast and lung cancers. xref xref However, germline pathogenic mutations have not been identified in patients with breast cancer. xref xref "
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 "
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"However, BAP1 can also form complexes with many other proteins, including the tumor suppressor BRCA1, host cell factor-1 (HCF-1), N-acetylglucosamine transferase, the forkhead box transcription factors FOXK1/2, MBD family proteins MBD5/6, transcription factor YY1 and ubiquitin conjugating enzyme UBE20 [XREF_BIBR, XREF_BIBR - XREF_BIBR]."