"Second, there are two major regulatory mechanisms to modulate MDM2 protein levels : p53 dependent transcriptional regulation and mTOR dependent translational control."
"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."
"In addition, MDM2 expression may be enhanced by mTOR through the translational machinery [XREF_BIBR]."
"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."
"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)."
"Moreover, in vivo inhibition of mTOR downregulates Mdm2 protein levels and induces p53 dependent apoptosis."
"mTOR activation increased expression of Mdm2, which is hereby identified as the necessary and sufficient ubiquitin E3 ligase for Drosha."
"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."