
IndraLab
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USP14 activates Proteasome. 26 / 27
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"Thus, USP14 creates a second kinetic checkpoint and drives the proteasome to choose between two alternative pathways of USP14-regulated conformational transitions—one that sterically impedes substrate commitment and the other that kinetically antagonizes RPN11 by outpacing the coupling of RPN11-directed deubiquitylation and substrate translocation, rather than directly inhibiting the DUB activity of RPN11."
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"A series of studies have demonstrated that Ubp6 and USP14 enhances the ATPase activity of proteasome and opens the 20S gate upon treatment with ubiquitin, ubiquitin protein conjugate or active site directed probes, such as ubiquitin aldehyde (Ubal) or ubiquitin vinyl sulfone (UbVS) (XREF_FIG A, right bottom panel) [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"In addition to this, other strategies under investigation for enhancing the activity of proteasome functioning include inhibition of USP14 that inhibits processing of proteasome employing pyrazolone and inhibition of the deubiquitinating enzyme that causes proteolysis of the proteasome [249, 250]."
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"Loss of Ubp6 function, for example, increases aneuploidy tolerance in yeast, presumably due to an elevated proteasome capacity for turning over higher protein levels, and pharmacological inhibition of Usp14 in human cells has been shown to stimulate proteasome activity XREF_BIBR - XREF_BIBR."