title: Proteasome as a Molecular Target of Microcystin-LR.
abstract: Proteasome degrades proteins in eukaryotic cells. As such, the proteasome is crucial in cell cycle and function. This study proved that microcystin-LR (MC-LR), which is a toxic by-product of algal bloom, can target cellular proteasome and selectively inhibit proteasome trypsin-like (TL) activity. MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the proteasome TL activity in the liver of the cyprinid rare minnow (Gobiocypris rarus). Protein degradation was retarded in GFP-CL1-transfected PC-3 cells because MC-LR inhibited the proteasome TL activity. Docking studies indicated that MC-LR blocked the active site of the proteasome β2 subunit; thus, the proteasome TL activity was inhibited. In conclusion, MC-LR can target proteasome, selectively inhibit proteasome TL activity, and retard protein degradation. This study may be used as a reference of future research on the toxic mechanism of MC-LR.
authors.affiliation: School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. zhuzhu@ustb.edu.cn.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. lizhang890125@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing 100083, China. shiguoqing@ustb.edu.cn.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Shi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003530:Cyprinidae; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D021122:Protein Subunits / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D049452:Green Fluorescent Proteins; D046988:Proteasome Endopeptidase Complex; C057862:cyanoginosin LR
keywords: mechanism; microcystin-LR; molecular docking; proteasome trypsin-like activity