Figure 2

From: Killers creating new life: caspases drive apoptosis-induced proliferation in tissue repair and disease

Figure 2

Mechanisms of caspase-dependent AiP. Apoptosis-induced proliferation may be induced by either initiator (a and b) or effector (ce) caspases. Activation of these caspases under certain conditions results in a variety of signaling cascades, producing a variety of growth factors and other mitogenic signals. (a and b) The Drosophila caspase Dronc is the only initiator caspase to date characterized as independently driving AiP. In transient regeneration (a), the active apoptosome including Dronc, triggers production of extracellular ROS and activates JNK, leading to production of the secreted mitogens Wingless (Wg) and Spitz (Spi). More sustained regeneration (b) requires additional input from recruited immune cells, signaling through the TNF homolog Eiger (Egr) and its receptor Grindelwald (Grnd), and possibly involves additional mitogens. (c–e) Effector caspases are implicated in AiP across the species, but examples shown here have confirmed the requirement of effector caspase activity. (c) In hydra, regeneration of an amputated head is dependent on caspase activity in the apoptotic cells at the regeneration site. These cells release the mitogen Wnt3. (d) The effector caspases Drice and DCP-1 are required for Hedgehog (Hh) production in Drosophila during AiP in maturing eye tissues. (e) In mice and human cell lines, following any number of injuries, including surgical resection, radiation or cytotoxic chemotherapies, caspase-3 cleaves a phospholipase A2 (iPLA2) triggering production of prostaglandin E2 (PGE2) which stimulates AiP. Caspase-3 also is required for VEGF-A production. Caspase-7 activates the kinase PKCδ, activating similar stress response pathways as seen in Drosophila