IndraLab

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USP7 inhibits TP53. 47 / 56
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"Our results support a new role for vIRF1 through deregulation of the deubiquitinating enzyme USP7 to inhibit p53 mediated antiviral responses."
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"Notably, selective dual inhibitors of USP7 and USP47 have been synthesized and induced accumulation of p53 and apoptosis in human cancer cell lines [XREF_BIBR]."
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"As p53 is activated by genotoxic stress and has a key role in genotoxic stress induced cell death, we reasoned that pharmacological inhibition of USP7 activity would potentiate p53 activity and result in increased chemosensitivity."
24136231
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"The inhibition of USP7 with HBX 41,108, a DUB to Hdm2 has shown to induce p53 dependent apoptosis with an IC in sub-micro-molar concentrations."
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"Notably, USP7 overexpression has been demonstrated to stabilize MDM2 and destabilize p53, promoting p53 proteasomal degradation and diminishing p53 tumor suppressor downstream networks (Li et al., 2004)."
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"On the other hand, by ubiquitinating itself, MDM2 targets itself for destruction and promotes the p53 tumor suppressor pathway, a process that can be antagonized by the deubiquitinase herpesvirus associated ubiquitin specific protease (HAUSP)."
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"Typically , USP7 could stabilize MDM2 by deubiquitination and subsequently promotes the degradation of p53 , causing the inhibition of apoptosis in cancer cells ( Bhattacharya et al. 2018 ) ."
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"Inhibition of USP7 induces p53-independent tumor growth suppression in triple-negative breast cancers by destabilizing FOXM1."
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"Although several Daxx interacting proteins are involved in critical cellular pathways regarding P53 degradation, such as ubiquitin-specific-processing protease 7 (USP7) and mouse double minute 2 (Mdm2) [XREF_BIBR, XREF_BIBR], it is still unclear whether Daxx has any role in tumorigenicity of OSCC."
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"Furthermore, HAUSP inhibition elevates p53 stability and might be beneficial for therapeutic purposes."
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"Collectively, we have demonstrated that inhibition of USP7 by a small-molecule inhibitor P22077 can result in reactivation of p53 and consequently inhibit tumor growth."
24136231
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"The essential role of USP7 during cell cycle progression and apoptosis has been reported by other groups : i ) USP7 knockdown leads to increased p53 expression and arrest of cell cycle ( Cummins et al ., 2004 ) , ii ) USP7 regulated various tumor-related factors expression ( p53 , Ki-67 ) in bladder cancer and prostate cancer ( Song et al ., 2008 ; Morra et al ., 2019 ) ."
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"This hypothesis is supported by our finding that proteasome inhibition with MG132 abrogated USP7 inhibition‐induced downregulation of MDM2 and upregulation of p53 in SnCs."
32064756
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"Partial reductions in HAUSP levels lead to destabilization of p53, whereas more complete reductions may cause MDM2 destabilization and p53 accumulation."
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"In addition, HAUSP dependent stabilization of Mdm2 and Mdmx might enhance degradation of p53 by the Mdm2 and Mdmx heterodimer."
20172729
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"HAUSP , which is localized in the nucleus , can prevent the degradation of p53 by deubiquitinating even under the circumstance of highly expressed Mdm2.120 ,218 Unlike HAUSP , USP10 is generally located in the cytoplasm ."
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"In addition, we showed that p53 induced by USP7 inhibition in SnCs localized partially to mitochondria, where it might induce SnC apoptosis by interacting with BCL‐XL and displacing BAK."
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"Knockdown of USP7 expression increases p53 expression and inhibits colon cancer cells proliferation ( Colland et al ., 2009 ) ."
34812471
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"USP7 counteracts autoubiquitylation of MDM2 , thereby promoting p53 degradation ."
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"Inhibition of USP7 activated p53 via suppressing deubiquitination, which led to down-regulation of TfR1, accompanied by the decreased ferroptosis and myocardial I/R injury."
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"In addition, USP7 is suppressed by various DUB inhibitors including HBX41108 and P22077, thereby regulating p53 [94-96]."
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"In cancer , USP7 could stabilize MDM2 by de-ubiquitination and subsequently promotes degradation of P53 specifically [ 12 ] ."
32002017
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"Therefore, we confirm that USP7 also as an oncogene inhibits p53 dependent apoptosis in melanoma, as in colon cancer."
33869052
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"Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines."
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"For example, expression of EBNA1 but not a USP7 binding mutant of EBNA1 in U2OS cells was shown to reduce the accumulation of p53 in response to DNA damage and subsequent apoptosis [XREF_BIBR]."
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"Here, we show that inhibitors of HAUSP and Nutlin-3 can synergistically activate p53 function and induce p53 dependent apoptosis in human cancer cells."
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"A class of dual small molecule inhibitors of USP7 and USP47 has been identified to promote p53 activity and apoptosis in MM and B-cell leukemia cells in vitro and xenograft models."
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"The essential role of USP7 during cell cycle progression and apoptosis has been reported by other groups: i) USP7 knockdown leads to increased p53 expression and arrest of cell cycle (Cummins et al., 2004), ii) USP7 regulated various tumor-related factors expression (p53, Ki-67) in bladder cancer and prostate cancer (Song et al., 2008; Morra et al., 2019)."
34812471
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"As p53 can antagonize the anti-apoptotic effects of Bcl-2 and Bcl-xL [XREF_BIBR], USP7 may inhibit the Bcl-2 and Bcl-xL anti-apoptotic effect by negatively regulating p53."
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"Here, we report that in response to DNA damage USP7 is downregulated by the ATM dependent protein phosphatase PPM1G, thus downregulating Mdm2 and activating the p53 response."
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"Thus, inhibiting HAUSP by small compound interference has been proposed as a rational therapeutic strategy to activate p53 in p53 wild type tumors."
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"For example, expression of EBNA1 but not a USP7 binding mutant of EBNA1 was shown to reduce the accumulation of p53 in response to DNA damage in U2OS cells [XREF_BIBR]."
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"More recently, it has been shown that a small molecule inhibitor of HAUSP, HBX41108, stabilizes p53 and induces p53 dependent apoptosis in cancer cell lines that retain wild-type p53 [XREF_BIBR]."
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"Hence, inhibition of Usp7 is thought to inactivate Mdm2 and thereby activate p53, resulting in inhibition of cell cycle progression and tumor cell apoptosis."
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"In cancer, USP7 could stabilize MDM2 by de-ubiquitination and subsequently promotes degradation of P53 specifically [12]."
32002017
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"To avoid complications associated USP7 inhibition-induced p53 accumulation, we knocked out p53 in both C3H10T1/2 and ST2 cells using CRISPR."
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"Inhibition of USP7 is expected to increase p53 levels , leading to anti-tumour activity [ 79 , 80 ] ."
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"Upon cellular stresses, such as DNA damage or oncogene activation, the TP53 degradation process is attenuated by USP7 and USP10, two deubiquitinating enzymes."
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"By either mechanism, our results establish that USP7 modulates the repressive H3K9me3 mark by protecting SUV39H1 from MDM2 mediated degradation and blocking aberrant p53 transactivation of target genes in unstressed p53 wt cells."
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"Furthermore, the abnormal embryos showed p53 staining in the remaining cells, suggesting loss of HAUSP caused accumulation of p53 (XREF_FIG)."
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"Overexpression of TSPYL5 suppresses p53 function and its target genes by regulating ubiquitin specific protease 7 (USP7) that cause p53 degradation."
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"26 Taken together, these studies suggest that USP7-MDM2-p53 is a critical axis that functions to limit the level of p53 in cells and that USP7 inhibition can result in p53 activation and cell death."
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"It seems that EBNA1 could strongly upregulate p53-inhibiting genes including HDAC1, MDM2, MDM4 , and USP7 ."
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"Increased ARF-BP1 and Mule degradation causes p53 stabilization, which is antagonized by the DUBs USP7 and USP4."
25806049
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"That is , by knocking down USP7 expression through targeted homologous recombination , Vogelstein and colleagues found that rather than stabilizing p53 , USP7 instead protects Mdm2 from auto-ubiquitination , thus indirectly triggering p53 degradation ."
32201366
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"The results also demonstrated that USP7 can upregulate MDM2 , and inhibit the expression of p53 ."
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"USP7 impairs the balance of the p53/MDM2 axis resulting in the proteasomal degradation of the p53 tumor suppressor, a process that can be reversed by small-molecule inhibitors of USP7."
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