Icad apoptosis
Although ICAD expression levels have been quantified in a variety of human cancer cells, the mechanism of ICAD gene regulation remains unknown. The apoptotic process is accompanied by shrinkage and fragmentation of the. DNA fragmentation factor is a heterodimer complex of the nuclease CAD and its specific inhibitor ICAD, which can be activated during apoptosis to induce DNA fragmentation. Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. During apoptosis, activated caspase-3 or -7 cleave DFF45/ICAD releasing active DFF40/CAD nuclease. DNA fragmentation factor subunit alpha (DFFA), also known as Inhibitor of caspase-activated DNase (ICAD), is a protein that in humans is encoded by the DFFA gene. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD. In non-apoptotic cells, DFF is a nuclear heterodimer consisting of a 45 kD chaperone and inhibitor subunit (DFF45)/inhibitor of CAD (ICAD-L) and a 40 kD nuclease subunit (DFF40/CAD)( Liu et al. These observations not only suggest that CAD activation drives apoptosis through a positive feedback loop, but also identify a unique suicide system that can be used for controlling gene-modified organisms. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA.
In the vertebrate cells, ectopic CAD activation triggered caspase activation and subsequent hallmarks of caspase-dependent apoptotic changes, including phosphatidylserine exposure and nuclear fragmentation. Our studies demonstrate that rapid ICAD depletion is sufficient to activate CAD and induce cell death in DT40 and yeast cells. Taking advantage of the auxin-inducible degron (AID) system, we have developed a suicide system with which ICAD is rapidly degraded in living cells in response to the plant hormone auxin. In particular, it has been unclear whether direct CAD activation in non-apoptotic living cells can trigger cell death. of ICAD by activated caspases causes the dissociation of the ICAD/CAD heterodimer and. Other aspects of CAD regulation are poorly understood. Programmed cell death or apoptosis leads to the activation of the. Although both ICAD-L and ICAD-S can bind and inhibit CAD, only ICAD-L was reported to be functional. ICAD has two isoforms: a functional isoform of 45kDa, ICAD-L/DNA fragmentation factor (DFF) 45 and a 35kDa isoform, ICAD-S/DFF35. CAD is normally activated in apoptosis as a result of caspase cleavage of its inhibitory chaperone ICAD. ICAD is the inhibitor of caspase-3-activated DNase which is a substrate that controls nuclear apoptosis. Caspase-activated DNase (CAD) is a major apoptotic nuclease, responsible for DNA fragmentation and chromatin condensation during apoptosis.