Historical Background
Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) was independently identified by two different groups as the third member of the tumor necrosis factor (TNF) super-family (Wiley et al. 1995; Pitti et al. 1996). It was soon described as capable of inducing apoptosis in transformed cells while sparing normal cells (LeBlanc and Ashkenazi 2003). Apo2L/TRAIL is a type-II membrane protein, composed of 281 amino acids and its gene, designated as TNFSF10, is located on human chromosome 3 at locus 3q26. Its C-terminal extracellular domain shares significant homology with other members of the TNF super-family, whereas the N-terminal does not. The polypeptide moiety of the Apo2L/TRAIL monomer has a predicted molecular mass of 32.5 kDa, but its mature, fully glycosylated form has a molecular mass of around 41 kDa....
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Anel A, Bosque A, Naval J, Pineiro A, Larrad L, Alava MA, et al. Apo2L/TRAIL and immune regulation. Front Biosci. 2007;12:2074–84.
Azijli K, Weyhenmeyer B, Peters GJ, de Jong S, Kruyt FA. Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family. Cell Death Differ. 2013;20:858–68. https://doi.org/10.31038/cdd.2013.28.
de Miguel D, Lemke J, Anel A, Walczak H, Martinez-Lostao L. Onto better TRAILs for cancer treatment. Cell Death Differ. 2016;4:174.
Gonzalvez F, Ashkenazi A. New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene. 2010.
Hellwig CT, Rehm M. TRAIL signaling and synergy mechanisms used in TRAIL-based combination therapies. Mol Cancer Ther. 2012;11:3–13. https://doi.org/10.1158/1535-7163.MCT-11-0434.
Jin Z, Li Y, Pitti R, Lawrence D, Pham VC, Lill JR, et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell. 2009;137:721–35. https://doi.org/10.1016/j.cell.2009.03.015.
Jouan-Lanhouet S, Arshad MI, Piquet-Pellorce C, Martin-Chouly C, Le Moigne-Muller G, Van Herreweghe F, et al. TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation. Cell Death Differ. 2012;19:2003–14.
Kantari C, Walczak H. Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta. 2011;1813:558–63. https://doi.org/10.1016/j.bbamcr.2011.01.026.
Lamhamedi-Cherradi SE, Zheng SJ, Maguschak KA, Peschon J, Chen YH. Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL−/− mice. Nat Immunol. 2003;4:255–60.
LeBlanc HN, Ashkenazi A. Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ. 2003;10:66–75. https://doi.org/10.1038/sj.cdd.4401187.
Merino D, Lalaoui N, Morizot A, Schneider P, Solary E, Micheau O. Differential inhibition of TRAIL-mediated DR5-DISC formation by decoy receptors 1 and 2. Mol Cell Biol. 2006;26:7046–55. https://doi.org/10.1128/mcb.00520-06.
Ozoren N, El-Deiry WS. Defining characteristics of Types I and II apoptotic cells in response to TRAIL. Neoplasia. 2002;4:551–7. https://doi.org/10.1038/sj.neo.7900270.
Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 1996;271:12687–90. https://doi.org/10.1074/jbc.271.22.12687.
Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, et al. FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity. 2000;12:599–609. https://doi.org/10.1016/s1074-7613(00)80211-3.
Takeda K, Hayakawa Y, Smyth MJ, Kayagaki N, Yamaguchi N, Kakuta S, et al. Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells. Nat Med. 2001;7:94–100.
Varfolomeev E, Maecker H, Sharp D, Lawrence D, Renz M, Vucic D, et al. Molecular determinants of kinase pathway activation by Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Biol Chem. 2005;280:40599–608. https://doi.org/10.1074/jbc.M509560200.
von Karstedt S, Conti A, Nobis M, Montinaro A, Hartwig T, Lemke J, et al. Cancer cell-autonomous TRAIL-R signaling promotes KRAS-driven cancer progression, invasion, and metastasis. Cancer Cell. 2015;27:561–73.
Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K, et al. Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med. 2007;13:1070–7. http://www.nature.com/nm/journal/v13/n9/suppinfo/nm1627_S1.htm
Wiley SR, Schooley K, Smolak PJ, Din WS, Huang C-P, JK N, et al. Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995;3:673–82.
Zerafa N, Westwood JA, Cretney E, Mitchell S, Waring P, Iezzi M, et al. Cutting edge: TRAIL deficiency accelerates hematological malignancies. J Immunol. 2005;175:5586–90.
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Martinez-Lostao, L., de Miguel, D., Anel, A., Naval, J. (2018). APO2L/TRAIL. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_2
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