IndraLab

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BAP1 activates INO80. 9 / 10
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"Importantly, Ino80 levels are often reduced in BAP1-null mesothelioma cells, which lack a BAP1 mediated Ino80 stabilization mechanism, and downregulated in BAP1 defective cancer cells in mesothelioma patients [XREF_BIBR]."
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"Importantly, a correlation was found between BAP1 and INO80 expression in mesothelioma, and re-expression of BAP1 in H226 cells exhibiting low levels of INO80 fully rescued the INO80 levels, showing that the low INO80 expression level in H226 cells was due to a lack of BAP1-mediated INO80 stabilization ."
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"Ino80 is downregulated in BAP1 defective mesothelioma, owing to the lack of a BAP1 mediated Ino80 stabilization mechanism, thus raising the possibility of a tumorigenic role for INO80 in this cancer."
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"While individual expression of CHIP and BAP1 increased Ino80, as expected, coexpression of these proteins increased endogenous Ino80 (XREF_FIG) and transfected Flag-Ino80 beyond the levels achieved by individual expression of either protein (XREF_FIG)."
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"Therefore, BAP1 promoted replication fork progression via dual mechanisms: stabilization via deubiquitination and recruitment of INO80 to the replication fork."
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"Conversely, knockdown of CHIP, BAP1, or both decreased Ino80 preferentially in the chromatin fractions (XREF_FIG)."
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"One reason for this could be that the simultaneous knockdown of CHIP and BAP1 decreased Ino80 only marginally compared to the individual knockdown, which is likely due to a limitation of siRNA knockdown."
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"By recruiting INO80 to the stalled forks, BAP1 allows stress induced stalled replication forks to restart, a mechanism that suppresses genome instability and thus cancer development."
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"Linked to this is the role of BAP1 in replication-coupled repair, where BAP1 aids to recruit and stabilise the chromatin remodeller INO80 to sites of DNA damage or replication stress, possibly to promote resection through its remodelling activity [116] (Figures 2A and 3A)."
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