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Mutated MDM2 inhibits TP53. 10 / 10
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"In agreement with this model, mdm2 mutants defective in p300 but not in p53 binding failed to mediate degradation of p53 and a p53 mutant unable to bind to the N-terminal E6 like domain of p300 was re[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Moreover, the RPL11 haploinsufficiency–induced p53 activation was prevented by the MDM2 mutation at both protein (Fig. 6E) and mRNA (Fig. 6, F and G) levels."
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"In contrast, the MDM2 mutants that enhance p53 degradation (W335L, S435R, M465I) would promote tumor development by maintaining p53 at low levels."
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"In the absence of antagonist, p53 function was reduced ~ 90% by wild-type and mutant HDM2."
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"The mutant MDM2 proteins were unable to inhibit p53 dependent transcription in vivo, which is consistent with prior indications that a physical interaction between the two proteins is required for MDM2 's inhibition of p53."
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"These results established the unique properties of the E2-binding mutant MDM2 that genetically separate MDM2-MDM4 E3 ligase activity from MDM2-MDM4 mediated suppression of p53 transcriptional transactivation."
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"As shown in Fig. 5 , overexpression of wild-type MDM2 reduced the protein level of TCAP and p53, but the reduction for TCAP did not appear to require the C-terminal RING finger domain of MDM2, as the [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Thus, it was found that an Mdm2 mutant lacking residues 222-272 also fails to drive p53 degradation, and actually promotes p53 stabilization [88]."
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"In contrast, the MDM2 mutants that failed to degrade p53 in our degradation assays generated fewer and smaller colonies than the wild-type MDM2 stable cells."
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"Importantly, the Deltap1-23A Mdm2 mutant interacts with p53 similarly to wild-type Mdm2 (XREF_SUPPLEMENTARY) and degrades p53 as efficiently as wild-type Mdm2 (XREF_SUPPLEMENTARY)."
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