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USP13 increases the amount of MCL1. 7 / 7
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"Interestingly, Zhang et al. showed that pharmacological inhibition of USP13 by a small-molecule inhibitor, spautin-1, markedly downregulated MCL1 protein levels and sensitized ovarian and lung cancer cells to ABT-263, a selective antagonist of BCL-2 and BCL-XL.We selected DUB3 as an ideal target in ovarian cancer due to its oncogenic functions in various cancer subtypes ."
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"We confirmed the siRNA screen results by transfecting each of the four oligos against USP13 into HEK293T cells, and indeed found that USP13 knockdown decreased the endogenous protein levels of MCL1, while modulating USP9X or OTUB2 with different siRNAs had no consistent effects on MCL1 expression."
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"Interestingly, over-expression or depletion of USP13 did not modulate Mcl-1 expression in HPV- C33A cells, suggesting that Mcl-1 expression is not regulated by USP13 in these cells."
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"In line with these observations, MCL1 protein levels were downregulated by depletion of USP9X but not USP13 (Figure S6D)."
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"Critically, treatment of USP13 depleted cells with the proteasome inhibitor MG132 rescued Mcl-1 protein levels, suggesting that USP13 protects Mcl-1 from proteasomal degradation."
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"Loss of USP13 significantly reduced Mcl-1 protein expression, without effecting MCL1 mRNA expression."
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"In addition, we explored whether pharmacological inhibition of USP13 downregulated MCL1 protein expression and synergistically kill tumor cells in combination with ABT-263."
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