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USP17L2 activates BRD4. 9 / 9
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"Interestingly, a recent study shows that a proficient expression of deubiquitinase DUB3 in prostate cancer can promote BRD4 stabilization and resistance to BETi ."
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"Likewise, DUB3 overexpression promoted BRD4 protein stabilization and accumulation, resulting in resistance to BET inhibitors 29 ."
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"We further showed that forced expression of DUB3 induced upregulation of BRD4 proteins in cultured cells and that elevation of DUB3 expression was correlated with a high level of BRD4 protein in a sub[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In contrast, knockdown of DUB3 by two independent shRNAs decreased the level of endogenous BRD4 proteins but had no overt effect on BRD4 mRNA expression in both PC-3 and DU145 cells."
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"Accordingly, overexpression of DUB3 increased the level of ectopically expressed full-length BRD4 protein in a dose dependent manner but had no effect on BRD4DeltaCTM mutant, BRD2 or BRD3 in PC-3 cell[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Since elevated levels of BRD4 confer resistance to BET inhibitors (references), DUB3 mediated BRD4 stabilization results in resistance to BRD4 inhibition in cancer [65]."
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"We demonstrated that knockdown of endogenous DUB3 by two independent shRNAs largely decreased BRD4 protein and that these effects were reversed by restored expression of DUB3-WT and the phospho mimick[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"DUB3 mediated BRD4 stabilization overcomes SPOP mediated degradation to confer BET inhibitor resistance."
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"Treatment of DU145 cells with PD0332991 decreased BRD4 protein levels in a time dependent manner, and the effect of PD0332991 was completely impeded by the proteasome inhibitor MG132, arguing that CDK[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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