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MDM2 decreases the amount of CDKN1A. 33 / 46
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"In its traditional pro-survival role, AKT activates MDM2 which in turn inhibits p53 and p21 expression leading to the inhibition of apoptosis."

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"18 In addition, it has been shown that mdm-2 could directly inhibit p21 expression, independent of p53."

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"Silencing Mdm2 or Akt1 upregulated p21 expression, whereas Akt1 overexpression downregulated p21 at the promoter and protein levels in p53WT cells."

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"Western blots revealed that the loss of one Mdm2 or Mdm4 gene copy modestly increased p21 levels, cells heterozygous for both Mdm2 and Mdm4 expressed slightly more p21, and Mdm4 −/− cells expressed th[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"We showed that loss of one copy of Mdm2 , or of one or both Mdm4 alleles, increased p21 levels and partially restored cycle control."

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"The overexpression of the exogenous Mdm2 gene further downregulated the level of cellular p53 protein, causing a low level of cellular p21 protein, while the cellular level of the CCDC106 protein was maintained at a low level independent of the expression of exogenous and endogenous Mdm2 (Fig. 4c)."

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"We verified that knockdown of Mdm2 upregulated the p53 and p21 protein levels."

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"It is known that the expression of p21 is negatively regulated by MDM2 and AKT 36."

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"As a confirmation of the effect of Nutlin3A, the data showed that exogenous HDM2 mediated decrease in P53 and P21 expression was partially blocked by Nutlin3A (XREF_FIG)."

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"In cells lacking p53, Mdm2 overexpression results in decreased p21 protein levels, whereas Mdm2 knockdown increases p21 protein levels and decreases proliferation [32,33]."

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"MDM2 shRNA1 knockdown increased p53 and p21 expression in wild-type p53 cell lines, induced p27 expression in MESO428 and JMN1B, and decreased cyclin D1 expression in MESO428 and MCF7, but had no effect on cyclin D1 expression in MESO924, MESO296, and JMN1B."

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"Intriguingly, overexpressing Mdm2 reversed p53 and p21 expression ( Fig. 4 G), further supporting that p53-p21 signal axis can be regulated by MDM2 in rat cells."

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"These results demonstrated that the inhibitory effect on cell growth by the down-regulation of MDM2 levels was not associated with the p14ARF status.A previous study showed that the inhibition of MDM2[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"As expected, inhibition of MDM2 with RG7388 induced p21 WAF1 and CIP1 expression by reactivating p53 in LNCaP cells due to strong inhibition of MDM2 [XREF_BIBR]."

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"Furthermore, inhibition of AKT signaling or MDM2 expression strongly restored p21 protein levels that were decreased by PSMC5 knockdown in H460 cells ( Fig. 4 ), indicating that the AKT-MDM2 pathway i[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"As expected, Mdm2 knockdown enhanced the levels of p53 and p21 (Fig. 4A, lanes 1 and 3)."

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"Next, we tested whether the inhibitors of Wip1 and Mdm2 are increasing p21 and Mdm2 levels in a p53 dependent fashion."

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"Similarly, MDM2 inhibition with MI-219 was shown to elevate p21 levels and produce p53 dependent sensitization of LNCaP prostate cancer cells to radiation, antiandrogen therapy, and the combination of the two."

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"MDM2 knockdown increased p53 and p21 expression, irrespective of p53 mutational status, in p53 wild-type LPS141 and MESO924."

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"Of note, the knockdown of MDM2 increased the expression of p21/CDKN1A in parallel with p53 and inhibited the growth of IOMM-Lee and A172 cells (Figure 2A,B), suggesting that both of these cell lines expressed functional MDM2 and p53 and also that the endogenous expression of MDM2 contributed to the inactivation of p53 in these cell lines."

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"The inhibition of MDM2 with anti-MDM2 antisense oligonucleotide or Short Interference RNA targeting MDM2 significantly elevated p21 protein levels in PC3 cells (p53 null)."

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"PD166866 and RG7112, an MDM2/p53 inhibitor, cooperatively inhibited the colony formation and distal seeding of LSCC cells (P < 0.01), and upregulated the expression of p53 and p21."

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"In both doxorubicin-untreated and -treated cells, overexpression of Mdm2 FL or MdmX FL led to decreased p21 protein levels."

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"In this study, we found that knockdown of MDM2 increases the level of p21 expression in cells and promotes cellular senescence."

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"A prediction from this hypothesis was that inhibition of MDM2 would restore p21 levels upon RITA treatment."

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"Additionally, MDM2 inhibition by Nutlin-3a markedly elevated p53 and p21 expression, increased cellular senescence, and induced the expression of inflammatory molecules including HMGB1 and IL-6."

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"Consequently, in HPAC cells, the levels of wild type p53 and p21 Waf1 and CIP1, both of which are negatively regulated by MDM2, 7 were elevated."

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"Activation of MDM2 through AKT signaling also suppresses the expression of p21 [ 48 ]."

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"Mdm2 has been shown to negatively regulate p21 protein levels in a p53 independent manner, which can account for this increase in the p53-null H1299 line."

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"When P-a were treated with Lipo246 EVs and SAR405838 for 96h, the EV inhibitory effect on p53 and p21 was abrogated (lane four) compared to P-a treated with Lipo246 EVs (in lane three), suggesting that uptake of MDM2 DNA by P-a inhibited p53 and p21 expression."

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"MDM2 inhibition with Nutlin-3a led to increased levels of p21 and MDM2 in all p53 cell lines."

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"As Mdm2 has been shown to reduce p21 protein levels under some conditions (45, 46), this may reflect impaired Mdm2 induction by the mutant (Figs."

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"As shown in Figure XREF_FIG, MDM2 suppression increased levels of p53 and p21 in all wt TP53 cells."