Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-induced cell death by modulating JNK activation
MST3 (mammalian sterile 20-like kinase 3) is a sterile 20 kinase reported to have a role in Fas-ligation- and staurosporine-induced cell death by unknown mechanism(s). We found that MST3-deficient cells are resistant to H2O2, which was reversed by reconstituting recombinant MST3. H2O2-induced JNK (c...
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| Published in | Bioscience reports Vol. 29; no. 6; pp. 405 - 415 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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01.12.2009
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| Abstract | MST3 (mammalian sterile 20-like kinase 3) is a sterile 20 kinase reported to have a role in Fas-ligation- and staurosporine-induced cell death by unknown mechanism(s). We found that MST3-deficient cells are resistant to H2O2, which was reversed by reconstituting recombinant MST3. H2O2-induced JNK (c-Jun N-terminal kinase) activation was greatly enhanced in shMST3 cells (a cell line treated with short hairpin RNA against MST3). Suppression of JNK activity by the inhibitor SP600125 or by dominant-negative JNK2 re-sensitized cells to H2O2. Furthermore, c-Jun Ser-63 phosphorylation was augmented in shMST3 cells, whereas JunAA (dominant-negative c-Jun) reduced H2O2 resistance, implicating an AP-1 (activator protein 1) pathway in H2O2-induced survival signalling. Total cytoprotective HO-1 (haem oxygenase 1) expression, which was attenuated by JunAA, was induced up to 5-fold higher in shMST3 cells compared with controls. Zinc protoporphyrin IX, a potent inhibitor of HO reversed the H2O2-resistance of shMST3 cells. Our results reveal that H2O2-induced MST3-mediated cell death involves suppressing both a JNK survival pathway and up-regulation of HO-1. |
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| AbstractList | MST3 (mammalian sterile 20-like kinase 3) is a sterile 20 kinase reported to have a role in Fas-ligation- and staurosporine-induced cell death by unknown mechanism(s). We found that MST3-deficient cells are resistant to H2O2, which was reversed by reconstituting recombinant MST3. H2O2-induced JNK (c-Jun N-terminal kinase) activation was greatly enhanced in shMST3 cells (a cell line treated with short hairpin RNA against MST3). Suppression of JNK activity by the inhibitor SP600125 or by dominant-negative JNK2 re-sensitized cells to H2O2. Furthermore, c-Jun Ser-63 phosphorylation was augmented in shMST3 cells, whereas JunAA (dominant-negative c-Jun) reduced H2O2 resistance, implicating an AP-1 (activator protein 1) pathway in H2O2-induced survival signalling. Total cytoprotective HO-1 (haem oxygenase 1) expression, which was attenuated by JunAA, was induced up to 5-fold higher in shMST3 cells compared with controls. Zinc protoporphyrin IX, a potent inhibitor of HO reversed the H2O2-resistance of shMST3 cells. Our results reveal that H2O2-induced MST3-mediated cell death involves suppressing both a JNK survival pathway and up-regulation of HO-1. |
| Author | Wu, Wei Ng, Jowin K W Choo, Poh-Heok Porter, Alan G Chen, Ce-Belle |
| Author_xml | – sequence: 1 givenname: Ce-Belle surname: Chen fullname: Chen, Ce-Belle email: ce-belle.chen@green.oxon.org organization: Division of Cancer and Developmental Cell Biology, Institute of Molecular and Cell Biology, ASTAR (Agency for Science, Technology and Research), Singapore. ce-belle.chen@green.oxon.org – sequence: 2 givenname: Jowin K W surname: Ng fullname: Ng, Jowin K W – sequence: 3 givenname: Poh-Heok surname: Choo fullname: Choo, Poh-Heok – sequence: 4 givenname: Wei surname: Wu fullname: Wu, Wei – sequence: 5 givenname: Alan G surname: Porter fullname: Porter, Alan G |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19604147$$D View this record in MEDLINE/PubMed |
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| Snippet | MST3 (mammalian sterile 20-like kinase 3) is a sterile 20 kinase reported to have a role in Fas-ligation- and staurosporine-induced cell death by unknown... |
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| StartPage | 405 |
| SubjectTerms | Apoptosis - physiology Cell Line, Tumor Enzyme Activation Heme Oxygenase-1 - metabolism Humans Hydrogen Peroxide - pharmacology JNK Mitogen-Activated Protein Kinases - metabolism Oxidative Stress - drug effects Oxidative Stress - physiology Phosphorylation Protein-Serine-Threonine Kinases - genetics Protein-Serine-Threonine Kinases - metabolism |
| Title | Mammalian sterile 20-like kinase 3 (MST3) mediates oxidative-stress-induced cell death by modulating JNK activation |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/19604147 |
| Volume | 29 |
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