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Caspase-2 pathways to apoptosis and cell cycle arrest. In response to cellular stresses PIDD activates caspase-2. Active caspase-2 cleaves Bid to form tBid, which induces mitochondrial outer membrane permeabilization. Active caspase-2 also cleaves MDM2 to form MDM2 p60, which binds to and stabilizes p53. p53 induces PIDD expression resulting in a feed-forward loop. Caspase-2 is also activated by ATM/ATR independently of p53 when Chk1 activity is repressed
