Icad antibody full#

Prolonged mitotic arrest can lead to DNA damage and p53 induction ( Lanni and Jacks, 1998 Dalton et al., 2007 Quignon et al., 2007), followed by cell cycle arrest or apoptosis. More speculatively, partial activation of CAD may explain the DNA-damaging effects of diverse cellular stresses that do not immediately trigger apoptosis. Increased DNA damage via caspases and CAD may be an important aspect of antimitotic drug action. This partly activates CAD, causing limited DNA damage and p53 induction after slippage. We conclude that prolonged mitotic arrest partially activates the apoptotic pathway.

Icad antibody full#

DNA damage was not due to full apoptosis, since most cytochrome C was still sequestered in mitochondria when damage occurred. These treatments also inhibited induction of p53 after slippage from prolonged arrest. This damage was inhibited by treatment with caspase inhibitors and by stable expression of mutant, noncleavable inhibitor of caspase-activated DNase, which prevents activation of the apoptosis-associated nuclease caspase-activated DNase (CAD). We detected DNA damage late in mitotic arrest and also after slippage. We investigated the cause of this induction. Live, single-cell imaging in human cancer cells responding to an antimitotic kinesin-5 inhibitor and additional antimitotic drugs revealed strong induction of p53 after cells slipped from prolonged mitotic arrest into G1. It can also cause DNA damage, but the relationship between these events has been unclear. Mitotic arrest induced by antimitotic drugs can cause apoptosis or p53-dependent cell cycle arrest.