ArticleInternational journal of biological sciences2011
Microcystin-LR (MCLR) induces a compensation of PP2A activity mediated by α4 protein in HEK293 cells.
Article in International journal of biological sciences, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 41 citations in OpenAlex.
- Microcystin-LR activates serine/threonine kinases and alters the phosphoproteome in human HepaRG cells.Toxicon : official journal of the International Society on Toxinology · 2024Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- In Vitro Toxicity Evaluation of Cyanotoxins Cylindrospermopsin and Microcystin-LR on Human Kidney HEK293 Cells.Toxins · 2022Article
- Review of Cyanotoxicity Studies Based on Cell Cultures.Journal of toxicology · 2022Review
- Microcystin Toxicokinetics, Molecular Toxicology, and Pathophysiology in Preclinical Rodent Models and Humans.Toxins · 2021Review
- Sub-chronic microcystin-LR renal toxicity in rats fed a high fat/high cholesterol diet.Chemosphere · 2021Article
- Sub-Chronic Microcystin-LR Liver Toxicity in Preexisting Diet-Induced Nonalcoholic Steatohepatitis in Rats.Toxins · 2019Article
- Mechanisms and Effects Posed by Neurotoxic Products of Cyanobacteria/Microbial Eukaryotes/Dinoflagellates in Algae Blooms: a Review.Neurotoxicity research · 2018Review
- Evaluation of the Direct and Indirect Regulation Pathways of Glutathione Target to the Hepatotoxicity of Microcystin-LR.BioMed research international · 2018Article
- Review
- Neuronal BC RNAs cooperate with eIF4B to mediate activity-dependent translational control.The Journal of cell biology · 2014Article
- Computer-aided targeting of the PI3K/Akt/mTOR pathway: toxicity reduction and therapeutic opportunities.International journal of molecular sciences · 2014Review
- Aggregate culture: A more accurate predictor of microcystin toxicity for risk assessment.Toxicon : official journal of the International Society on Toxinology · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein phosphatase 2A (PP2A) is a major protein phosphatase with important cell functions. Known and utilized as a potent inhibitor of PP2A, microcystin-LR (MCLR) targets PP2A as a core element that affects numerous cellular mechanisms. But apart from direct inhibition, the exact effect of MCLR on PP2A in cell is largely unknown, specifically with regard to cellular response and autoregulation. Here, we show that a low concentration of MCLR stimulates, rather than inhibits, PP2A activity in HEK293 cells. Immunoprecipitation and immunofluorescence assays reveal that the catalytic subunit and a regulatory subunit of PP2A, termed α4, dissociate from inactive complex upon MCLR exposure, suggesting that the released catalytic subunit regains activity and thereby compensates the activity loss. At high concentrations of MCLR, PP2A activity decreases along with dissociation of the core enzyme and altered post-translational modification of its catalytic subunit. In addition, the dissociation of α4 and PP2A may contribute to destabilization of HEK293 cells cytoskeleton architecture, detachment to extracellular matrix and further anoikis. Our data provide a novel PP2A upregulation mechanism and challenge the recognition of MCLR only as a PP2A inhibitor in cells.
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