IndraLab

Statements

USP4 binds FKBP*. 10 / 10
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"After two hours, FKBP*-USP4(C311S) levels were approximately 39 % of that observed in vehicle-treated cells, whereas levels of wild-type FKBP*-USP4 were about 86 % of the vehicle control."
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"These data strongly support the idea that catalytically active FKBP*-USP4 and FLBP*-USP15 resist PROTAC-mediated degradation through auto-deubiquitylation."
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"Both FKBP*-USP4 and FKBP*-USP15 levels were greater than 80 % that of vehicle-treated cells after two hours, in stark contrast to the rapid degradation of FKBP*-USP11."
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"After 24 hours, FKBP*-USP4, FKBP*-USP15 and FKBP*-UCHL1 levels had dropped to around 9 %, 23 % and 28 %, respectively, of that observed in vehicle-treated cells ( xref – xref )."
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"FKBP*-USP4 and -USP15 actively resist degradation through auto-deubiquitylation."
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"To investigate whether the less robust degradation of USP4, USP15 and UCHL1 was due to auto-deubiquitylation, we made mutant constructs in which the catalytic cysteine was replaced with a serine or alanine residue (FKBP*-USP4(C311S), FKBP*-USP15(C298A) and FKBP*-UCHL1(C90A))."
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"Next, the degradability of the FKBP*-USP4, -USP15 and -UCHL1 fusions was evaluated."
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"Treatment of both FKBP*-USP4(C311S) and FKBP*-UCHL1(C90A)-expressing cells with dTAG-13 resulted in greater depletion of the mutant construct compared to wild type DUB across all the concentrations tested ( xref and xref )."
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"At 500 nM dTAG-13, mutant FKBP*-USP4(C311S) levels were about 8 % of that in vehicle-treated cells."
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"In cells treated with 500 nM dTAG-13, FKBP*-USP4 levels were about 63 % that of vehicle-treated cells ( xref )."
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