Caspase activation via Dependence Receptors in the absence of ligand

Stable Identifier
R-HSA-418889
Type
Pathway
Species
Homo sapiens
Synonyms
Ligand-independent caspase activation via DCC
ReviewStatus
5/5
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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.
Literature References
PubMed ID Title Journal Year
12011067 Mediation of the DCC apoptotic signal by DIP13 alpha

Wu, R, Yao, F, Liu, J, Finley RL, Jr, Morgan, M, Chen, YQ, Thorburn, A

J Biol Chem 2002
12598906 p53RDL1 regulates p53-dependent apoptosis

Matsuda, K, Tanikawa, C, Arakawa, H, Fukuda, S, Nakamura, Y

Nat Cell Biol 2003
15310786 Role of the dependence receptor DCC in colorectal cancer pathogenesis

Mehlen, P, Fearon, ER

J Clin Oncol 2004
10348349 Induction of apoptosis and G2/M cell cycle arrest by DCC

Pong, RC, Cipriano, SC, Yao, F, Hsieh, JT, Krepulat, F, Chen, YQ, Fang, B

Oncogene 1999
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