IndraLab

Statements

USP7 inhibits PTEN. 10 / 11
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"Since we previously demonstrated that USP7 plays an essential role in the regulation of PTEN compartmentalization in CML [XREF_BIBR, XREF_BIBR], we sought to investigate whether USP7 functionally inactivates PTEN in CLL through PTEN nuclear exclusion."
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"Therefore, we speculated that USP7 inhibition may promote PTEN reactivation and consequently cancer selective apoptotic induction, without affecting normal cells."
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"USP7 has been shown to inactivate several tumor suppressors including P53, FOXO4 (Forkhead box O4) and PTEN (phosphatase and tensin homolog deleted on chromosome ten) through different mechanisms, which lead to tumorigenesis [XREF_BIBR - XREF_BIBR]."
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"In contrast, USP7 reduced nuclear localization of PTEN in PC3 cells without affecting total PTEN protein levels (XREF_FIG), consistent with previously reported findings 18."
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"Our data demonstrate that USP7 is responsible for PTEN nuclear exclusion with consequent impairment of its tumor suppressive functions and that USP7 inhibition restores PTEN nuclear pool and its oncosuppressive activity in the context of CLL."
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"In this respect, the PTEN and FOXO4 tumor suppressors are inactivated by USP7 induced nuclear export (Song et al., 2008; van der Horst et al., 2006)."
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"USP13 increases PTEN stability [126] , whereas USP7 reverses monoubiquitylation and nuclear accumulation of PTEN [125] ."
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"From a functional point of view, USP7 inhibition restores PTEN localization in CLL."
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"It was also reported that USP7 inhibition (P5091) restores PTEN nuclear pool and its onto suppressive activity in chronic lymphocytic leukemia (Carrà et al., 2017)."
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"Since we previously demonstrated that USP7 plays an essential role in the regulation of PTEN compartmentalization in CML [ xref , xref ], we sought to investigate whether USP7 functionally inactivates PTEN in CLL through PTEN nuclear exclusion."
28418900