IndraLab

Statements


USP8 activates EGFR. 20 / 22
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"This current study showed that the EGFR, PI3K, and NF-κB signaling is downregulated and upregulated in PCa by USP8 silencing and overexpressing, respectively ( Figure 4 )."

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"Other studies have suggested that mutations in USP8 reduce the degradation of EGFR, such as HER-2 and HER-3, thereby promoting tumor progression."

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"Nevertheless, both AMSH [31, 34, 35] and UBPY [32, 33, 36-38] have been reported to increase EGFR down-regulation."

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"USP8 knockdown leads to reduce EGFR protein and inhibits ACTH secretion."

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"Whereas USP8 variants increase EGFR signaling in cultured cells, such an effect has not been consistently shown in vivo, suggesting that the effect is small or temporary or that other factors [XREF_BIBR] are involved in increased ACTH production and/or proliferation of USP8 mutation positive tumors."

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"USP8 depletion inhibits EGFR degradation and causes accumulation of ubiquitinated proteins on enlarged endosomes 11, 12."

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"These binding reactions provide a scenario in which UBPY could aid transit of EGFR to ESCRT-III by helping to displace STAM2 from HD-PTP."

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"Our previous results have shown that Usp8 tyrosine phosphorylation upon EGF induced stimulation is EGFR- and Src- tyrosine kinase dependent [41]."

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"One report concludes that UBPY negatively regulates degradation of the epidermal growth factor receptor (EGFR), which is downregulated via MVB sorting and lysosomal degradation."

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"As USP8 silencing significantly inhibited the PCa cell growth, proliferation, and metastasis and induced apoptosis and suppressed NF-kB signal activation by decreasing EGFR and PI3K, the USP8-specific inhibitor might be a novel therapeutic target to suppress PCa cell growth, proliferation, and metastasis."

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"USP8 depletion accelerates receptor turnover, whereas loss of hepatocyte growth factor regulated substrate (Hrs) rescues this phenotype, indicating that USP8 protects EGFR from degradation via an Hrs dependent pathway."

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"Previous work reported that USP8 depletion severely inhibits EGFR degradation 11."

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"In contrast, the USP8-specific siRNA reduced EGFR and PI3K, suppressing the NF-kB signal."

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"Finally, depletion of endogenous UBPY by RNA interference resulted in elevated ubiquitination and accelerated degradation of EGF activated EGFR."

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"We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR."

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"In other studies, both AMSH XREF_BIBR, XREF_BIBR and UBPY XREF_BIBR, XREF_BIBR, XREF_BIBR have been reported to increase EGFR down-regulation."

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"Depletion of UBPY, another DUB that associates with ESCRT components, has been shown to both accelerate and slow the rate of EGFR degradation."

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"It is thought that the mutations in USP8 cause enhanced EGFR signaling and are closely associated with development of Cushing disease."

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"By doing so, UBPY promotes the transfer of EGFR to late acting ESCRT complexes, while simultaneously facilitating the removal of ubiquitin from EGFR prior to its deposition into ILVs."

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"Previous studies have shown that USP8 depletion causes EGFR accumulation in early endosomes and inhibits downstream degradation due to general defects in endosomal sorting 11."