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USP4 activates CTNNB1. 11 / 15
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"In the present study, we found that the USP4 and beta-catenin axis was involved in metastatic potential through USP4 mediated stabilization of beta-catenin and that knockdown of USP4 and beta-catenin suppressed the metastatic potential including clonogenicity, migration, and invasion, and induced MET by downregulating ZEB1 expression."
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"However, stabilized β-catenin was partially affected by the USP4 expression level ( Figure 2 F), and the catalytically defective C311A USP4 was able to activate β-catenin to some extent ( Figure 2 A)."
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"These results confirm that USP4 knockdown suppresses the transcriptional activity of beta-catenin, thereby supporting the suggestion that USP4 functions as a positive regulator of the WNT and beta-cat[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"However, USP4 had no effect on the stability of GSK3beta, a negative regulator of beta-catenin, suggesting that USP4 enhances the stability and activity of beta-catenin not by affecting beta-catenin r[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"In addition to these newly identified nuclear functions, both USP4 and USP15 are well known to function in the cytosol, i.e. USP4 modulates the Wnt and beta-catenin, NF-kappaB, p53 and TGF-beta signaling pathways while USP15 performs functions in the TGF-beta receptor and NF-kappaB signaling pathways."
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"For instance, USP4 promote tumor progression by regulating beta-Catenin Signaling XREF_BIBR."
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"The assay results revealed that transcriptional activity increases in proportion to the amount of USP4 in the nucleus, which suggests that USP4 enhances beta-catenin activity by facilitating its trans[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"This observation raised the possibility that USP4 dependent activation of beta-catenin is not only caused by the catalytic activity of USP4 but also mediated by another mechanism such as a nuclear tra[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Therefore, it can be speculated that USP4 promotes brain metastasis of LUAD cells by stabilizing the β-catenin protein74."
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"Interestingly, it was also found that knockdown of USP4 decreased the level of beta-catenin protein without changes in its mRNA level (XREF_FIG)."
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"This observation raised the possibility that USP4-dependent activation of β-catenin is not only caused by the catalytic activity of USP4 but also mediated by another mechanism such as a nuclear transp[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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