IndraLab

Statements

USP28 inhibits FBXW7. 16 / 16
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"Loss of the deubiquitinase Usp28 monoallele stabilizes and facilitates Fbw7 mediated substrate degradation, whereas, complete knockout of Usp28 promotes the degradation of Fbw7, leading to the accumulation of Fbw7 substrates."
30881487
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"For Myc, we also examined the effects of knock-down of USP28, a Ub specific protease that antagonizes Fbw7 dependent Myc destruction [XREF_BIBR]."
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"Other proteins regulating C-MYC stability include : CIP2A, a C-MYC-interacting protein that specifically inhibits PP2A activity against C-MYC; USP28, a de-ubiquitinating enzymes that antagonizes FBW7 and promotes C-MYC stability and TRUSS, a receptor for DDB1 (damage specific DNA binding protein 1)-CUL4 (Cullin 4) E3 ligase complex."
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"A study has proposed a novel mechanism by which USP28 upregulates angiogenesis by antagonizing GSK-3beta (glycogen synthase kinase-3beta) and FBW7 dependent degradation of HIF-1alpha (hypoxia inducible factor-1alpha), a major regulator of angiogenesis, carcinogenesis, and various processes by which cells adapt to hypoxic conditions."
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"Consequently, half of the normal dose of Usp28 (in the Usp28 +/- cells) is adequate to maintain stable Fbw7 but is not sufficient to antagonize Fbw7 mediated substrate degradation."
25437563
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"Unexpectedly, we found that genetic deletion of Usp28 rescued the lethality of Fbw7 deficient primary fibroblasts."
25716680
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"Moreover, GSK3beta and FBW7 dependent HIF-1alpha degradation can be antagonized by the USP28 (ubiquitin specific peptidase-28), suggesting that FBW7 and USP28 could reciprocally regulate cell migration and angiogenesis in a HIF-1alpha-dependent manner [XREF_BIBR]."
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"On the other hand, downregulation of Fbw7, induced by Usp28 loss is either not sufficient to promote embryonic lethality, associated with Fbxw7 knockout, or does not occur in lineages, in which Fbw7 i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25437563
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"Finally, Fbw7 activity is antagonized by the ubiquitin-specific proteases Usp28 and Usp36, which may be readily amenable to inhibition with small molecules."
26459133
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"The Usp28 deubiquitinase antagonizes Fbw7 mediated turnover of multiple oncoproteins, including Myc, Jun, and Notch, and promotes tumorigenesis in the intestine."
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"Therefore, while heterozygousity can destabilize MYC, complete deletion of USP28 triggers Fbw7 auto-destruction, resulting in the stabilization of Fbw7 substrates including MYC in specific tissues.106 Thus, the USP28-Fbw7α interplay dictates MYC stability and activity in the nucleoplasm and involves fine stoichiometry of the two opposing enzymes."
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"Steady-state levels of Fbw7 in Usp28 -/- MEFs were rescued by MG132 treatment, demonstrating that Fbw7 was degraded by the proteasome in the absence of Usp28."
25437563
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"In contrast, Fbw7-associated DUBs have the potential to antagonize ubiquitination of multiple substrates.Fbw7-mediated degradation of Myc is antagonized by Usp28 and Usp36 [99,100] ."
26459133
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"In tumor cells, USP28 antagonizes the activity of the F-box and WD repeat domain containing 7 (FBXW7) to promoting the stability of c-Myc."
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"Interestingly, Usp28 antagonizes the action of Fbw7 without directly binding Myc."
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"Although single allele deletion of Usp28 allows FBXW7 mediated substrate degradation, it has little effect on FBXW7 stability."
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