BAP1
BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)
a deubiquitylase associated with multi-protein complexes that regulate the cell cycle, cellular differentiation, cell death, gluconeogenesis and the DNA damage response [Pubmed]; crucial for histone H2A deubiquitination [Pubmed]
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role in cancer | TSG |
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cell division control | important in the G1/S transition, regulates the levels of cell cycle proteins by affecting E2F1-dependent S-phase gene expression [Pubmed] |
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types of alteration in cancer | altered by Copy Number Loss, mutation, and/or loss of protein expression in over 70% of tumour samples in malignant peritoneal mesothelioma [Pubmed] |
genome instability and mutations
inactivation results in chromosome instability caused by lack of gamma-tubulin deubiquitination during mitosis in breast adenocarcinoma MDA-MB-468 cell line [Pubmed]
escaping programmed cell death
suppression of deubiquitinating activity or nuclear localisation of BAP1 reduces its ability to promote apoptosis in NSCLC NCI-H226 cell line [Pubmed]; KD causes drop in the protein levels of survivin, a member of anti-apoptotic proteins and increases apoptosis in melanoma [Pubmed]; localised at ER, it regulates the release of calcium ions from the ER to cytoplasm that promotes apoptosis; reduced levels of BAP1 at ER result in resistance to apoptosis in primary fibroblasts an mesothelial cells [Pubmed]
proliferative signalling
promotes cancer cell proliferation by deubiquitinating and stabilising KLF5 in breast cancer [Pubmed]
invasion and metastasis
KD reduces the invasiveness of cells in uveal melanoma OCM1 and OM431 cell line [Pubmed]; promotes metastasis by deubiquitinating and stabilising KLF5, KD decreases cell migration and invasiveness in vitro and inhibits lung metastasis in mouse model in breast cancer [Pubmed]
change of cellular energetics
overexpression decreases ubiquitination of PGC-1alpha, protecting it from degradation and promoting gluconeogenesis [Pubmed]