Endogenous galectin-3 determines the routing of CD95 apoptotic signaling pathways.
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.
Fukumori
Tomoharu
T
Tumor Progression and Metastasis Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Takenaka
Yukinori
Y
Oka
Natsuo
N
Yoshii
Tadashi
T
Hogan
Victor
V
Inohara
Hidenori
H
Kanayama
Hiro-Omi
HO
Kim
Hyeong-Reh Choi
HR
Raz
Avraham
A
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*
D037502:Galectin 3; D019014:fas Receptor; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases