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USP14 inhibits HMBS. 7 / 7
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"For example, USP14, known to inhibit protein degradation via the UPS by cleaving the K48-linked ubiquitin chain from the target, could also modulate the autophagy by promoting the K63-linked deubiquitination of specific targets, such as Beclin1."
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"Taken together, these data show that phosphorylation of USP14 by Akt is important for this kinase to negatively regulate the UPS in a ubiquitin dependent manner."
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"We recently reported that inhibition of the deubiquitinating enzyme USP14, which is known to enhance both the UPS and autophagy, increases lifespan and rescues the pathological phenotype of two Drosophila models of PD."
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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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"In a previous work, we showed that inhibition of Usp14 enhances the activity of the ubiquitin-proteasome system (UPS), autophagy and mitophagy, and abolishes motor symptoms of two well-established fly models of PD that accumulate dysfunctional mitochondria."
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"For example, researchers have discovered inhibitors, like b-AP15 to covalent inhibition of both USP14 and UCHL5 to induce the cathepsin-dependent apoptosis by inhibiting the UPS system [131]."
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"Interestingly, it appears USP14 not only negatively regulates the UPS, but also negatively regulates autophagy through removing Lys63 linked ubiquitin chains from the autophagy regulator Beclin-1 [XREF_BIBR]."
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