title: Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways.
abstract: Studies of CD95 (APO-1/Fas), a member of the death receptor family, have revealed that it is involved in two primary CD95 apoptotic signaling pathways, one regulated by the large amount of active caspase-8 (type I) formed at the death-inducing signaling complex and the other by the apoptogenic activity of mitochondria (type II). To date, it is still unclear which pathway will be activated in response to an apoptotic insult. Here, we demonstrate that the antiapoptotic molecule galectin-3, which contains the four amino acid-anti-death-motif (NWGR) conserved in the BH1 domain of the Bcl-2 member proteins, is expressed only in type I cells. Transfection of galectin-3 cDNA into galectin-3 null cells (type II) resulted converting them to type I apoptotic phenotype. In addition, we show that galectin-3 is complexed with CD95 in vivo identifying galectin-3 as a novel CD95-binding partner that determines which of the CD95 apoptotic signaling pathways the cell will select.
authors.affiliation: Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: Tomoharu
authors.initials: T
authors.lastname: Fukumori
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Takenaka
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshii
authors.forename: Victor
authors.initials: V
authors.lastname: Hogan
authors.forename: Hidenori
authors.initials: H
authors.lastname: Inohara
authors.forename: Hiro-Omi
authors.initials: HO
authors.lastname: Kanayama
authors.forename: Hyeong-Reh Choi
authors.initials: HR
authors.lastname: Kim
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014162:Transfection; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
chemical_list: D037502:Galectin 3; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases