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USP28 deubiquitinates FBXW7. 21 / 21
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"USP28 can antagonize the process of FBW7 autoubiquitination, which can promote the degradation of BRAF and then lead to the attenuation of MAPK signaling [16, 115], suggesting that USP28 can suppress cell proliferation."
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"USP28 deubiquitinates and stabilizes FBW7 resulting in enhanced degradation of FBW7 substrates."
29880484
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"In addition, the autocatalytic ubiquitylation of Fbw7 can be antagonized by the deubiquitinase Usp28 [XREF_BIBR]."
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"USP28 deubiquitinates and stabilizes FBW7, allowing the WD40 repeat sequence in FBW7 to bind and degrade substrates containing Cdc4 phosphorylation motifs, and it was found that the Cdc4 phosphorylation structural domains are widely present in human RAF subtypes."
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"However, it has recently emerged that USP28 also directly de-ubiquitinates Fbw7, thereby controlling its protein stability [95] ."
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"Ubiquitin specific peptidase 28 (USP28), a deubiquitinating enzyme can also repress autocatalytic ubiquitination and degradation of FBXW7 (Diefenbacher et al., 2014; Schulein-Volk et al., 2014)."
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"For instance, USP7 can promote cancer development by downregulating p53 levels through deubiquitination of mouse double minute 2 (MDM2); lysine 63 deubiquitinase (CYLD), which is frequently mutated in nasopharyngeal carcinoma, inhibits cell invasion and metastasis by interfering with the NF-κB signaling pathway; USP28 is an oncogenic factor that deubiquitinates F-box and WD repeat domain containing 7 (FBXW7), thereby enhancing the stability of RAF family members and inhibiting activation of the MEEK pathway."
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"Indeed, wild-type Usp28, but not the catalytically inactive C171A mutant, promoted Fbw7 deubiquitination in vivo."
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"To test whether Usp28 directly deubiquitinates Fbw7, we used an in vitro assay with immunopurified SCF (Fbw7) and recombinant E1 and E2 enzymes, which leads to the accumulation of autoubiquitinated Fb[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Usp28 preferentially deubiquitinates Fbw7 and at intermediate levels maintains stable Fbw7 but does not allow excessive Fbw7 substrate stabilization."
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"As USP28 deubiquitinates and stabilizes FBW7, allowing the FBW7 and SCF ligase complex to bind and degrade substrates containing a Cdc4 phosphodegron motif, we hypothesized that forced expression of USP28 would target BRAF for degradation."
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"Indeed, experiments in MEFs and human tumor cells demonstrate that Usp28 directly deubiquitinates and stabilizes Fbw7."
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"We discuss mechanisms that regulate ubiquitination by <span class="match term1">Fbw7</span>, including ubiquitin-specific proteases such as <span class="match term0">USP28</span> that counteract <span class="match term1">Fbw7</span> activity and thereby stabilise oncoproteins."
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"It was recently shown that the deubiquitinase Usp28 deubiquitinates and stabilizes Fbxw7 [XREF_BIBR]."
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"USP28 interacts with and deubiquitinates FBW7 leading to the stability of FBW7 and consequently promoting degradation of FBW7 substrates."
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"On the other hand, in circumstances where USP28 levels are high, USP28 can deubiquitinate and stabilize both FBW7 and its bound substrate."
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"At the same time, Usp28 blocks autocatalytic ubiquitination of Fbw7 [103] ."
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"For example, the deubiquitinase USP28 antagonizes FBXW7 autocatalytic ubiquitination and stabilizes both FBXW7 and its substrates [58]."
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"In this setting, USP28 deubiquitinates the SCF component FBW7, allowing FBW7 to act as a substrate recognition factor targeting substrates for proteosomal mediated degradation."
29880484
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"In addition, USP28 antagonizes FBW7 mediated ubiquitination and stabilizes HIF-1alpha [XREF_BIBR, XREF_BIBR]."
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"However, in some cell types, USP28 can also deubiquitinate and stabilise FBXW7 itself [14], leading to the downregulation of FBXW7 targets [15]."
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