IndraLab

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USP14 activates MAPT. 8 / 8
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"13 IU1 , an inhibitor of USP14 , can increase UPS activities , promote Tau degradation , and enhance mitochondrial elimination in neuronal cells.14 , 15 , 16 Similarly , dysregulation of USP14 has been reported in several tumors , including breast cancer , lung adenocarcinoma , and epithelial ovarian cancer.17 , 18 , 19 However , whether USP14 is involved in preeclampsia remains elusive ."
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"Intriguingly, Lee et al. demonstrated that IU1, a selective small-molecule inhibitor of USP14, accelerated proteasomal degradation of tau and TDP-43, which have been implicated in neurodegenerative diseases XREF_BIBR."
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"Knockdown of USP14 also marginally reduced tau (Figure S1A and S1B), consistent with USP14 aptamers enhancing tau degradation through the proteasome (Lee et al., 2015)."
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"In agreement with the function of USP14, we observed that coexpression of USP14-WT resulted in the elevated levels of both the longest isoform of human MAPT (MAPT-WT) and its aggregation-prone P301L m[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"192 Conversely, IU1, a small molecule inhibitor of USP14, stimulated the degradation of tau."
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"Moreover, IU1-47, a small molecule inhibitor of USP14, was also shown to accelerate the degradation of tau protein (Table 2) (Boselli et al., 2017)."
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"This result is also consistent with Boselli et al.’s observation that USP14 inhibition enhances tau degradation in cultured neurons [213]."
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"Although pharmacological inhibitors of USP14's ubiquitin-hydrolase activity reduced microtubule associate protein tau, tar DNA binding protein, and prion protein in culture, the effect was similar in wild type and USP14-deficient neurons, thus impacting their use for specifically evaluating USP14 in a therapeutic manner."
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