The fungal chimerolectin MOA inhibits protein and DNA synthesis in NIH/3T3 cells and may induce BAX-mediated apoptosis

Gabriele Cordara; Harry C Winter; Irwin J Goldstein; Ute Krengel; Kirsten Sandvig

doi:10.1016/j.bbrc.2014.04.043

The fungal chimerolectin MOA inhibits protein and DNA synthesis in NIH/3T3 cells and may induce BAX-mediated apoptosis

Biochem Biophys Res Commun. 2014 May 16;447(4):586-9. doi: 10.1016/j.bbrc.2014.04.043. Epub 2014 Apr 18.

Authors

Gabriele Cordara¹, Harry C Winter², Irwin J Goldstein², Ute Krengel³, Kirsten Sandvig⁴

Affiliations

¹ 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.
² Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0606, USA.
³ Department of Chemistry, University of Oslo, PO Box 1033 Blindern, 0315 Oslo, Norway. Electronic address: ute.krengel@kjemi.uio.no.
⁴ 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.

PMID: 24747075
DOI: 10.1016/j.bbrc.2014.04.043

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.

Keywords: Cystein protease; Cytotoxicity; Fungal chimerolectin; Hydrolytic enzyme; NIH/3T3 cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Agglutinins / metabolism
Agglutinins / pharmacology
Agglutinins / toxicity
Amino Acid Substitution
Animals
Apoptosis / drug effects*
Apoptosis / physiology*
Fungal Proteins / metabolism
Fungal Proteins / pharmacology*
Fungal Proteins / toxicity
Genetic Variation
Lectins / metabolism
Lectins / pharmacology
Lectins / toxicity
Marasmius / chemistry
Marasmius / genetics
Mice
NIH 3T3 Cells
Nucleic Acid Synthesis Inhibitors / pharmacology
Nucleic Acid Synthesis Inhibitors / toxicity
Protein Synthesis Inhibitors / pharmacology
Protein Synthesis Inhibitors / toxicity
bcl-2-Associated X Protein / metabolism*

Substances

Agglutinins
Bax protein, mouse
Fungal Proteins
Lectins
Nucleic Acid Synthesis Inhibitors
Protein Synthesis Inhibitors
bcl-2-Associated X Protein