title: The fungal chimerolectin MOA inhibits protein and DNA synthesis in NIH/3T3 cells and may induce BAX-mediated apoptosis.
abstract: The Marasmius oreades mushroom agglutinin (MOA) is a blood group B-specific lectin carrying an active proteolytic domain. Its enzymatic activity has recently been shown to be critical for toxicity of MOA toward the fungivorous soil nematode Caenorhabditis elegans. Here we present evidence that MOA also induces cytotoxicity in a cellular model system (murine NIH/3T3 cells), by inhibiting protein synthesis, and that cytotoxicity correlates, at least in part, with proteolytic activity. A peptide-array screen identified the apoptosis mediator BAX as a potential proteolytic substrate and further suggests a variety of bacterial and fungal peptides as potential substrates. These findings are in line with the suggestion that MOA and related proteases may play a role for host defense.
authors.affiliation: Department of Chemistry, University of Oslo, PO Box 1033 Blindern, 0315 Oslo, Norway; Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cordara
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Winter
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
authors.forename: Irwin J
authors.initials: IJ
authors.lastname: Goldstein
authors.affiliation: Department of Chemistry, University of Oslo, PO Box 1033 Blindern, 0315 Oslo, Norway. Electronic address: ute.krengel@kjemi.uio.no.
authors.forename: Ute
authors.initials: U
authors.lastname: Krengel
authors.affiliation: Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, 0379 Oslo, Norway; Department of Biosciences, University of Oslo, PO Box 1041 Blindern, 0316 Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Norway. Electronic address: kirsten.sandvig@ibv.uio.no.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Sandvig
mesh_terms: D000373:Agglutinins / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D005656:Fungal Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014644:Genetic Variation; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D055433:Marasmius / Q000737:chemistry / Q000235:genetics; D051379:Mice; D041681:NIH 3T3 Cells; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology / Q000633:toxicity; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: D000373:Agglutinins; C494827:Bax protein, mouse; D005656:Fungal Proteins; D037102:Lectins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D051028:bcl-2-Associated X Protein
keywords: Cystein protease; Cytotoxicity; Fungal chimerolectin; Hydrolytic enzyme; NIH/3T3 cells