Gene interactions and pathways from curated databases and text-mining
Mol Cell Biol 2004, PMID: 15199126

Phospholipase D elevates the level of MDM2 and suppresses DNA damage-induced increases in p53.

Hui, Li; Abbas, Tarek; Pielak, Rafal M; Joseph, Troy; Bargonetti, Jill; Foster, David A

Phospholipase D (PLD) has been reported to generate survival signals that prevent apoptosis induced by serum withdrawal. We have now found that elevated expression of PLD also suppresses DNA damage-induced apoptosis. Since DNA damage-induced apoptosis is often mediated by p53, we examined the effect of elevated PLD expression on the regulation of p53 stabilization. We report here that PLD suppresses DNA damage-induced increases in p53 stabilization in cells where PLD has been shown to provide a survival signal. Elevated expression of PLD also led to increased expression of the p53 E3 ubiquitin ligase MDM2 and increased turnover of p53. PLD1-stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen-activated protein kinase pathway. Although PLD did not activate the phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway activate the basal levels of PI3K activity were partially required for PLD1-induced increases in MDM2. These data provide evidence that survival signals generated by PLD involve suppression of the p53 response pathway.

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Text Mining Data

MDM2 → PLD: " Elevated expression of PLD also led to increased expression of the p53 E3 ubiquitin ligase MDM2 and increased turnover of p53 "

p53 ⊣ mTOR: " PLD1 stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen activated protein kinase pathway "

p53 ⊣ PLD1: " PLD1 stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen activated protein kinase pathway "

MDM2 → mTOR: " PLD1 stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen activated protein kinase pathway "

MDM2 → PLD1: " PLD1 stimulated increases in MDM2 expression and suppression of p53 activation were blocked by inhibition of mTOR and the mitogen activated protein kinase pathway "

MDM2 → PLD: " Although PLD did not activate the phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway activate the basal levels of PI3K activity were partially required for PLD1 induced increases in MDM2 "

MDM2 → PLD1: " Although PLD did not activate the phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway activate the basal levels of PI3K activity were partially required for PLD1 induced increases in MDM2 "

Manually curated Databases

No curated data.