Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53

Sodium orthovanadate inhibits p53-mediated apoptosis.

Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) alpha. We compared the effects of vanadate to PFTalpha...

MDC1 cleavage by caspase-3: a novel mechanism for inactivating the DNA damage response during apoptosis.

Recently, we identified the "apoptotic ring," containing phosphorylated histone H2AX (γ-H2AX), as an early chromatin modification during apoptosis. Because γ-H2AX initiates the DNA damage response (DDR), we tested whether the apoptotic H2AX response leads to the full recruitment of the DDR factors that normally coordinate DNA repair and cell-cycle checkpoints. We show that the apoptotic H2AX re...

p53-independent apoptosis limits DNA damage-induced aneuploidy.

DNA damage or unprotected telomeres can trigger apoptosis via signaling pathways that directly sense abnormal DNA structures and activate the p53 transcription factor. We describe a p53-independent mechanism that acts in parallel to the canonical DNA damage response pathway in Drosophila to induce apoptosis after exposure to ionizing radiation. Following recovery from damage-induced cell cycle ...

Molecular and Cellular Pathobiology MDC1 Cleavage by Caspase-3: A Novel Mechanism for Inactivating the DNA Damage Response during Apoptosis

Recently, we identified the "apoptotic ring," containing phosphorylated histone H2AX (g-H2AX), as an early chromatin modification during apoptosis. Because g-H2AX initiates the DNA damage response (DDR), we tested whether the apoptotic H2AX response leads to the full recruitment of the DDR factors that normally coordinate DNA repair and cell-cycle checkpoints. We show that the apoptotic H2AX re...

Sodium Orthovanadate Is a Bifunctional Inhibitor of Transcription-Dependent and -Independent p53-Mediated Apoptosis Supplemental Data