IndraLab

Statements

Notch increases the amount of TP53. 8 / 8
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"Chemical inhibition of Notch signaling in both human and mouse keratinocytes did not reduce the expression of p53 at the protein or mRNA level either before or after transduction with the reprogramming factors (XREF_FIG and XREF_SUPPLEMENTARY)."
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"In fact, upregulation of p53 expression by Notch activation, at the level of gene transcription, has also been observed in glioma cells 80, but sustained Notch signalling in this case is important for survival 50."
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"To directly investigate whether Notch target genes can induce p53 transcription, we cotransfected the p53 reporter plasmid and plasmids encoding individual Hey and Hes proteins into MuSCs."
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"Notch ligand mediated activation dramatically decreased pMDM2 Ser260 without altering total MDM2 levels, and markedly increased p53 protein levels (XREF_FIG)."
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"Furthermore, Notch activation in neural progenitor cells leads to elevated levels of nuclear p53 and transcriptional upregulation of the target genes Bax and Noxa, and the promotion of apoptotic cell death by Notch activation is completely suppressed by p53 deficiency."
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"Re-expression of p53 (wt) in p53 (null) cells restored the inhibition of proliferation by activated Notch."
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"Thus, IKAROS may not trigger Tp53 repression, but the increase of H3K79 methylation and the ' additive effect ' observed in Ik Null / OP9-DL1 suggest that, by controlling H3K79me2 levels, IKAROS prevents the NOTCH dependent induction of Tp53 transcriptional overexpression, which is likely linked to a variation in the control of transcriptional elongation."
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"To further examine the ability of Notch signaling to induce p53 expression, we transduced and sorted AML cells in vitro and found significantly increased levels of p53 protein, along with increased cleaved caspase3 and PARP1 (XREF_FIG)."
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