PMID- 20841567 OWN - NLM STAT- MEDLINE DCOM- 20110110 LR - 20160513 IS - 1937-9145 (Electronic) IS - 1945-0877 (Linking) VI - 3 IP - 139 DP - 2010 Sep 14 TI - Characterization of the extrinsic apoptotic pathway in the basal chordate amphioxus. PG - ra66 LID - 10.1126/scisignal.2000906 [doi] AB - The death receptor (DR)-mediated apoptosis pathway is thought to be unique to vertebrates. However, the presence of DR-encoding genes in the sea urchin and the basal chordate amphioxus prompted us to reconsider, especially given that amphioxus contains 14 DR proteins and hundreds of death domain (DD)-containing adaptor proteins. To understand how the extrinsic apoptotic pathway was originally established and what the differences in signaling are between invertebrates and vertebrates, we performed functional studies of several genes that encode DDs in the amphioxus Branchiostoma belcheri tsingtauense (Bbt). First, we observed that the increased abundance of Bbt Fas-associated death domain 1 (BbtFADD1) in HeLa cells resulted in the formation of death effector filamentous structures in the cytoplasm and the activation of the nuclear factor kappaB pathway, whereas BbtFADD2 protein was restricted to the nucleus, although its death effector domain induced apoptosis when in the cytoplasm. We further demonstrated that formation of a FADD-caspase-8 complex recruited amphioxus DR1 (BbtDR1), which bound to the adaptor proteins CRADD or TRAF6 (tumor necrosis factor receptor-associated factor 6) to convey distinct signals, ranging from apoptosis to gene activation. Thus, our study not only reveals the evolutionary origin of the extrinsic apoptotic pathway in a basal chordate but also adds to our understanding of the similarities and differences between invertebrate and vertebrate FADD signaling. FAU - Yuan, Shaochun AU - Yuan S AD - State Key Laboratory of Biocontrol, National Engineering Research Center of South China Sea Marine Biotechnology, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, 135 West Xingang Road, Guangzhou 510275, P. R. China. FAU - Liu, Huiling AU - Liu H FAU - Gu, Ming AU - Gu M FAU - Xu, Liqun AU - Xu L FAU - Huang, Shengfeng AU - Huang S FAU - Ren, Zhenhua AU - Ren Z FAU - Xu, Anlong AU - Xu A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100914 PL - United States TA - Sci Signal JT - Science signaling JID - 101465400 RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (NF-kappa B) RN - 0 (TNF Receptor-Associated Factor 6) RN - EC 3.4.22.- (Caspase 8) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Caspase 8/genetics/*metabolism MH - Chordata, Nonvertebrate/embryology/genetics/*metabolism MH - Fas-Associated Death Domain Protein/genetics/*metabolism MH - HEK293 Cells MH - HeLa Cells MH - Humans MH - NF-kappa B/genetics/*metabolism MH - Protein Structure, Tertiary MH - Signal Transduction/physiology MH - TNF Receptor-Associated Factor 6/genetics/*metabolism EDAT- 2010/09/16 06:00 MHDA- 2011/01/11 06:00 CRDT- 2010/09/16 06:00 PHST- 2010/09/16 06:00 [entrez] PHST- 2010/09/16 06:00 [pubmed] PHST- 2011/01/11 06:00 [medline] AID - 3/139/ra66 [pii] AID - 10.1126/scisignal.2000906 [doi] PST - epublish SO - Sci Signal. 2010 Sep 14;3(139):ra66. doi: 10.1126/scisignal.2000906.