UNC5A binds NRAGE Caspase cleavage of DCC DCC interacts with DIP13alpha Caspase-9 binds DCC:DIP13alpha complex Activation of caspase-3 Caspase cleavage of UNC5B DAPK binds UNC5B Caspase cleavage of UNC5A PathwayStep4437 PathwayStep4439 PathwayStep4438 PathwayStep4440 PathwayStep4443 PathwayStep4444 PathwayStep4441 PathwayStep4442 Role of DCC in regulating apoptosis Authored: Garapati, P V, 2008-07-16 14:42:16 Edited: Garapati, P V, 2008-07-30 10:24:23 In the presence of Netrin1, DCC and UNC5 generate attractive and repulsive signals to growing axons. In the absence of Netrin-1, DCC induces cell death signaling initiated via caspase cleavage of DCC and the interaction of caspase-9. Recent reports have shown that UNC5 receptors similarly induce apoptosis in the absence of Netrin-1. These reactions proceed without a requirement for cytochrome c release from mitochondria or interaction with apoptotic protease activating factor 1 (APAF1). DCC thus regulates an apoptosome-independent pathway for caspase activation. DCC and UNC-5 are hence defined as dependence receptors. Dependence receptors exhibit dual functions depending on the availability of ligand. They create cellular states of dependence on their respective ligands by either inducing apoptosis when unoccupied by the ligand, or inhibiting apoptosis in the presence of the ligand. Pubmed10348349 Pubmed12011067 Pubmed12598906 Pubmed15310786 Reactome Database ID Release 43418889 Reactome, http://www.reactome.org ReactomeREACT_22128 Reviewed: Cooper, HM, 2010-02-16