IndraLab

Statements

MTOR increases the amount of MDM2. 12 / 12
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"Second, there are two major regulatory mechanisms to modulate MDM2 protein levels : p53 dependent transcriptional regulation and mTOR dependent translational control."
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"MTOR stimulates the expression of MDM2 oncoprotein, which ubiquitinates Drosha and leads to the inhibition of miRNA biogenesis in response to energy deprivation (22)."
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"Conversely, the mTOR pathway modulates the protein level of MDM2."
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"Moreover, in vivo inhibition of mTOR downregulates Mdm2 protein levels and induces p53 dependent apoptosis."
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"MTOR activation increased expression of Mdm2, which is hereby identified as the necessary and sufficient ubiquitin E3 ligase for Drosha."
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"Consistently, it was found that in different ccRCC cell lines, the activation of mTOR promotes the expression of E3 ubiquitin-protein MDM2, which, in turn, induces p53 ubiquitination and degradation by proteasome [34]."
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"In addition, even in the absence of increased transcription, as in the case of Tp53 -/- background, mTOR activation still increased Mdm2 protein levels (XREF_FIG), suggesting that mTOR increases Mdm2 protein levels by p53 dependent and p53 independent mechanisms."
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"The increased activity of mTOR kinase enhances the expression of E3 ubiquitin ligase MDM2 that in turn promotes p53 ubiquitination, leading to its degradation by proteasome machinery in a network involving p70S6K."
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"To find out how inhibition of PI3K and mTOR inhibited MDM2 expression, we performed Western blot analysis with lysates prepared from cells treated with BEZ235."
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"Furthermore, the decreased activity of mTOR in these cells caused a significant reduction in the expression of MDM2 protein (XREF_FIG C) that in turn induced a rising of p53 levels, not detected in control cells (XREF_FIG A and B)."
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"In addition, a dual inhibitor of pan-PI3K and mTOR, DS-7423, decreased the phosphorylation level of MDM2, and induced TP53-mediated apoptosis in TP53 wild-type CCOC cells [ 14 ]."
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"In addition, MDM2 expression may be enhanced by mTOR through the translational machinery [XREF_BIBR]."
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