ICAD (inhibitor of caspase-activated DNase, also known as DFFA)
ICAD is the physiological inhibitor of CAD, the nuclease responsible for executing DNA fragmentation during apoptosis.
• Caspase-mediated cleavage of ICAD is a key regulatory step that unleashes CAD activity during apoptosis.
Its dysregulation (either up‐ or down‐regulation) has been linked to altered apoptotic responses, genomic instability, and ultimately clinical outcomes.
Either overexpression or underexpression can disrupt this balance:
▪ Overexpression may blunt the full execution of apoptosis in response to stresses (e.g., chemotherapy).
▪ Underexpression may lead to unscheduled or incomplete apoptosis, which in some scenarios might paradoxically fuel genomic instability.
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