title: Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release.
abstract: Galectin-7 is normally expressed in all types of stratified epithelia, but is significantly down-regulated in squamous cell carcinomas. This protein was recently found to be highly inducible by p53 in a colon carcinoma cell line, DLD-1, and designated as PIG1 (for p53-induced gene 1). We studied transfectants of HeLa and DLD-1 cells ectopically expressing this protein and found that they were more susceptible to apoptosis than control transfectants. This was observed in apoptosis induced by mechanistically distinct stimuli, suggesting that galectin-7 acts on a common point in the apoptosis signaling pathways. Further analyses of actinomycin D-induced apoptosis demonstrated that galectin-7 expression causes enhanced caspase-3 activity and poly(ADP-ribose) polymerase cleavage, and the potentiation of apoptosis by galectin-7 was completely abrogated by a caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone. In addition, galectin-7 transfectants displayed accelerated mitochondrial cytochrome c release and up-regulated JNK activity upon apoptosis induction. Several lines of evidence indicate that the effect on apoptosis is not due to the lectin functioning extracellularly through interactions with cell surface glycoconjugates. In fact, this lectin is found to localize in nuclei and cytoplasm of the transfectants and the transformed keratinocyte line HaCaT. Therefore, galectin-7 is a pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c release. DNA microarray analysis revealed genes that are differentially expressed between galectin-7 and control transfectants. Some of them are potentially contributory to this lectin's proapoptotic function and these include redox-related genes monoamine oxidase B, ryanodine receptor 2, and glutathione S-transferase Mu 3.
authors.affiliation: Divisions of Allergy and Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA. ichiro@liai.org
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kuwabara
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Kuwabara
authors.forename: Ri-Yao
authors.initials: RY
authors.lastname: Yang
authors.forename: Martin
authors.initials: M
authors.lastname: Schuler
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Hsu
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D003574:Cytochrome c Group / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D004789:Enzyme Activation; D037161:Galectins; D005786:Gene Expression Regulation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D003574:Cytochrome c Group; D037161:Galectins; C092525:LGALS7 protein, human; D037102:Lectins; D011994:Recombinant Proteins; D003609:Dactinomycin; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases