Figure 3

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

Figure 3

Regulation of caspases in AiP. Caspase activation may lead to apoptotic cell death or AiP. The exact mechanisms that direct caspase activity toward death or proliferative functions are not yet clear. When considering what is known regarding one of the better characterized pathways, the Dronc-dependent AiP in Drosophila epithelium, there are several possible regulatory mechanisms which could direct Dronc toward AiP. (a) Direct biochemical modification of caspases: Non-degradative mono-ubiquitinylation of Dronc inhibits both apoptotic and AiP activity. (b) Direction of caspases by adaptors or scaffolds: other non-apoptotic functions of Dronc rely on adaptors to localize the caspase to the non-apoptotic target. It is possible that Dronc-mediated AiP may be facilitated by an as of yet unidentified adaptor or scaffolding protein. (c) Feedback loops allow for amplification (green arrows) or inhibition (orange lines): positive feedback from JNK upregulating the pro-apoptotic factor hid increases Dronc activity and yields a robust AiP response. Negative feedback from EGFR signaling can inhibit Hid activity, potentially dampening the AiP response. As new downstream targets are uncovered for both initiator and effector caspase-dependent AiP, we will likely develop a better understanding of how a balance among these varying positive and inhibitory signals drive caspases towards a proliferative function