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BAP1 inhibits SLC7A11. 18 / 18
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"It was reported that the BRCA1-associated protein 1 (BAP1) tumor suppressor is also able to promote ferroptosis by repressing SLC7A11 [41]."
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"Further mechanistic studies demonstrated that BAP1 suppresses SLC7A11 expression partly by deubiquitinating histone 2A ubiquitination to promote ferroptosis ."
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"In addition, we studied how BAP1 coordinates with other transcription factors to regulate SLC7A11 expression and show that BAP1 mediated SLC7A11 repression does not require NRF2 and ATF4 transcription factors."
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"It has been recently reported that BAP1 facilitates lipid peroxidation and promotes ferroptosis through repressing SLC7A11 [24]."
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"Genomic analyses together with robust statistics have revealed that the restoration of BAP1 facilitates the formation of the polycomb repressive deubiquitinase (PR-DUB) complex and inhibits ubiquitinated histone 2A (H2Aub) occupancy on the SLC7A11 promoter."
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"As a deubiquitinating enzyme , BAP1 inhibits the expression of SLC7A11 by reducing the ubiquitination of H2A to inhibit the activity of SLC7A11 promoter ( 23 ) ."
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"Both BAP1 and PRC1 ( the main H2Aub ubiquitin ligase ) inhibit the expression of SLC7A11 [ 54 ] ."
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"Together, our data suggested a model that the BAP1 containing PR and DUB complex binds on the SLC7A11 promoter, where BAP1 removes ubiquitin from H2Aub, and BAP1 dependent H2Aub reduction on SLC7A11 is associated with BAP1 mediated SLC7A11 repression."
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"Several studies have revealed that BAP1 can inhibit ubiquitinated histone 2A (H2Aub) occupancy on the SLC7A11 promoter (Zhang et al., 2018)."
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"The knockdown of SLC7A11 in UMRC6 cells (a BAP1-deficient renal cancer cell line) marginally affects cancer cell proliferation, suggesting that the BAP1-mediated tumor suppression through regulating SLC7A11 [80]."
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"Although the precise mechanism by which BAP1 induces SLC7A11 repression needs further elucidation , it was proposed that BAP1 , a H2A deubiquitinase , represses SLC7A11 expression by regulating the levels of H2A ubiquitination ( H2Aub ) on the SLC7A11 promoter ( Figure 2 ) [ 41 ] ."
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"Epigenetically , BAP1 inhibits SLC7A11 expression through de-ubiquitinating H2A [ 13 ] , while chromatin remodeling factor ARID1A increases SLC7A11 expression [ 14 ] ."
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"Analysis of our H2Aub ChIP-seq data revealed that restoration of BAP1 WT, but not BAP1 C91A, markedly decreased H2Aub occupancy at both the promoter and gene body of SLC7A11 (XREF_FIG), which was further confirmed by H2Aub ChIP assay on the SLC7A11 promoter and representative exons (XREF_FIG and XREF_SUPPLEMENTARY)."
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"In this manner , BAP1 reduces SLC7A11 expression and cysteine uptake , leading lipid peroxidation upregulation and the ferroptosis induction ( 71 ) ."
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"Two key tumor suppressor proteins , p53 ( TP53 ) ( Jiang et al ., 2015 ) and BAP1 ( Zhang et al ., 2018a ) , independently suppress SLC7A11 expression ."
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"Although the precise mechanism by which BAP1 induces SLC7A11 repression needs further elucidation, it was proposed that BAP1, a H2A deubiquitinase, represses SLC7A11 expression by regulating the levels of H2A ubiquitination (H2Aub) on the SLC7A11 promoter (Figure 2) [41]."
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"Among these genes, SLC7A11 (encoding the Solute Carrier Family 7 Member 11), an antiporter that imports cystine and exports glutamate, was repressed by BAP1."
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"In addition, Zhang et al. discovered that another tumor suppressor BAP1 promoted ferroptosis and inhibited the growth of cancer cells by inhibiting SLC7A11 (49)."
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