IndraLab

Statements

IU1 activates USP14. 6 / 6
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"To verify whether this shRNA effect is dependent on inhibition of the deubiquitinating activity of USP14, we used IU1, a potent pharmacological inhibitor that selectively inhibits USP14 by preventing its docking on the proteasome [XREF_BIBR], and tested the effect of USP14 inhibition by IU1 on the AR expression in breast cancer cells."
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"Consistent with these findings, the Wnt3a CM induced expression of Wnt target genes, such as Nkd1 and Lef1, was significantly impaired in Usp14 -/- MEFs or wild-type MEFs treated with IU1 (XREF_FIG)."
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"Notably, IU1 only promoted degradation in Usp14 murine embryonic fibroblasts but not in Usp14 cells, suggesting that this compound functions specifically through USP14."
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"By inhibiting the deubiquitinating activity of USP14, IU1 would presumably prevent the rescue of some ubiquitinated neurotoxic proteins at the proteasome (such as tau and ataxin-3), leading to their degradation."
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"The inhibitor IU1 blocks the activity of USP14 only in the presence of the proteasome , suggesting that it binds only to the activated enzyme ."
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"When usp14 -/- MEFs were treated with IU1, no effect on Tau was observed, indicating that IU1 enhances Tau degradation through inhibiting Usp14 (XREF_FIG)."
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