IU1 is a cell-permeable, reversible and selectiveproteasome inhibitor of human USP14 with IC50 of 4.7 μ M, 25-fold selective to IsoT.
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Usp14, a proteasome-associated deubiquitinating enzyme, can impede the degradation of ubiquitin-protein conjugates, both in vivo and in vitro. IU1 inhibits the catalytic activity of proteasome-associated Usp14 in vitro, with an IC50 of 4-5 μM. IU1 specifically binds to the activated form of Usp14 and may inhibit it by preventing its docking on the proteasome. However, direct tests of this scenario yielded negative results. Usp14 inhibition is rapidly established upon IU1 addition and rapidly reversed upon its removal. IU1 also promotes the degradation of Sic1, a CDK inhibitor from S. cerevisiae [1].
体外研究
Usp14, a proteasome-associated deubiquitinating enzyme, can impede the degradation of ubiquitin-protein conjugates, both in vivo and in vitro. IU1 inhibits the catalytic activity of proteasome-associated Usp14 in vitro, with an IC50 of 4-5 μM. IU1 specifically binds to the activated form of Usp14 and may inhibit it by preventing its docking on the proteasome. However, direct tests of this scenario yielded negative results. Usp14 inhibition is rapidly established upon IU1 addition and rapidly reversed upon its removal. IU1 also promotes the degradation of Sic1, a CDK inhibitor from S. cerevisiae [1].
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