IndraLab

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P5091 increases the amount of TP53. 6 / 6
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"P5091 (XREF_TABLE) actively inhibits USP7 at concentrations as low as 5-10 microM in the cellular environment, resulting in HDM2 polyubiquitination and accelerated degradation by the proteasome, and consequently increased steady-state protein levels of p53 and p21."
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"P5091 increased p53 and p21 protein levels in a time dependent fashion in the wild-type TP53 cells, TC32 and TC138 (XREF_FIG)."
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"6 This suggests that although P5091 increases p53 levels, its cytotoxic activity is not solely dependent on p53, indicating that P5091-induced cytotoxicity is mediated only in part via p53."
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"Further, we found through flow cytometry that a low dose of P5091 can cause early apoptosis of senescent HDF cells ( Fig. 3 E and G) and increase the expression of the apoptosis marker c-PARP1 and the[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Mechanistic studies further show that P5091 triggered apoptosis in MM cells is associated with 1) activation of caspase-8, caspase-9, caspase-3, and PARP; and 2) downregulation of USP7 substrate HDM2, as well as increased expression of p53 and p21."
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"P53 levels were slightly increased by HDM2-siRNA knockdown, and further upregulated by P5091 treatment."
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