IndraLab

Statements


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"Among these, Usp8/UbpY interacts with and is phosphorylated by activated epidermal growth factor receptor (EGFR), but its precise function in EGFR-signaling remains to be established."

sparser
"The potential mechanisms for the selective activation of the USP8-EGFR axis in the two types of diseases."

sparser
"USP8 is recruited to the EGFR via multiple interactions including binding of the USP8 DUB domain to ubiquitinated EGFR and recruitment of USP8 to the EGFR on endosomal membranes via the USP8 N-terminal domain [ xref ]."

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No evidence text available

reach
"In EGF stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"Under serum starvation – a standard method to promote ciliogenesis – this EGFRUSP8 signalling is reduced, allowing cilia formation to occur ( xref )."

sparser
"Regarding why the USP8-EGFR axis shows such a significant difference in pathway activation between benign pituitary adenomas and malignant tumors, there is actually still a lack of direct mechanism verification and clear preclinical studies."

sparser
"Therefore, in cancer, the USP8-EGFR axis may work synergistically with the oncogenic mutations of the core genes of the related signaling pathways."

sparser
"Given the differences in the tumor microenvironment between pituitary adenomas and cancers, the USP8-EGFR axis is highly likely to be affected differently in various tumor microenvironments, resulting in variations in the activation of downstream pathways."

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sparser
"USP8 interacts with the epidermal growth factor receptor, and regulates proliferation and differentiation."

sparser
"In hepatocellular carcinoma, the USP8-EGFR axis can activate three key signaling pathways: Raf/MEK/ERK, PI3K/AKT/mTOR, and JAK/STAT, working together to drive tumor progression [ xref ]."

sparser
"The percentage of EGFR-positive tumors was much lower in our cohort than in a published cohort, in which USP8 mutations were associated with higher EGFR expression [ xref ]."

sparser
"UBPY binds to endocytosed EGFR and deubiquitinates it on early endosomes [10] ."

sparser
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18] ."

sparser
"Immunoblotting of the precipitates with anti-FLAG antibody showed that wild-type UBPY and UBPY S680A bind to EGFR with similar efficiency upon EGF stimulation ( Supplementary Fig. S2 ), indicating th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

trips
"In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR."

sparser
"When overexpressed in HeLa cells, USP8 mutations were associated with reduced EGFR ubiquitination and degradation as compared to WT controls."

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"Furthermore, we demonstrate that optimal Usp8 tyrosine phosphorylation is not necessary for binding of Usp8 to EGFR."

sparser
"USP8 interacts with many substrates such as the epidermal growth factor receptor, an essential regulator of proliferation and differentiation, and regulates endosomal trafficking by ubiquitin-mediated sorting of the endocytosed cargoes ( xref ; xref ; xref )."

sparser
"We have previously shown that UBPY binds and deubiquitinates ligand-activated EGFR at early endosomes [10] ."

sparser
"However, the level of UBPY S680A binding to EGFR was comparable to that of wild-type UBPY ( Supplementary Fig. S2 )."

sparser
"Because USP8 has been reported to regulate a number of cancer targets including EGFR, xref – xref we first explored whether USP8 might interact with EGFR in NSCLCs, H1299 and H1650 cells."

reach
"We therefore examined whether the binding of UBPY to EGFR is indirect and mediated by 14-3-3 proteins which normally exist as a dimer [18]."

reach
"Immunoblotting of the precipitates with anti-FLAG antibody showed that wild-type UBPY and UBPY S680A bind to EGFR with similar efficiency upon EGF stimulation, indicating that the interaction between [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"On the other hand, 14-3-3zeta has been reported to bind ligand activated EGFR [25], raising the possibility that the interaction between UBPY and activated EGFR is mediated by the 14-3-3 dimer."

sparser
"By conducting an Immunoprecipitation assay, we found an interaction between endogenous USP8 and EGFR in both cell lines, confirming that EGFR is a USP8’s client protein ( xref )."

reach
"It is not clear why the data of XREF_BIBR showed an opposite effect on EGFR by USP8, but it is supported by their observations that upon EGF stimulation, USP8 directly binds EGFR."

sparser
"In sharp contrast to this, in pituitary adenomas, the USP8-EGFR axis does not participate in most of the aforementioned complex oncogenic signaling pathways."

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sparser
"Overall, these results support and extend our previous model that Usp8 and EGFR associate via multiple molecular interactions."

sparser
"Moreover, the USP8-EGFR axis specifically focuses on the regulation of the pro-opiomelanocortin (POMC)-ACTH axis."

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No evidence text available

sparser
"This finding extends our previous observations that Usp8 is tyrosine phosphorylated upon stimulation of the EGFR and that Usp8 is recruited to the EGFR via multiple interactions including (direct) bin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

reach
"By conducting an Immunoprecipitation assay, we found an interaction between endogenous USP8 and EGFR in both cell lines, confirming that EGFR is a USP8 's client protein (XREF_FIG)."

sparser
"Furthermore, mutation of S680 resulted in enhanced Usp8 activity towards EGFR, although the EGFRUsp8 interaction itself was not affected by S680 mutation."