Caspase-2 is a negative regulator of necroptosis
The role of caspase-2 in cell death regulation remains largely unknown. In this study we have analyzed the involvement of caspase-2 in RIPK1-regulated necrosis (necroptosis) in human ovarian carcinoma cells. We show that these cells undergo necroptosis upon treatment with the DNA damaging drug cispl...
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Veröffentlicht in: | The international journal of biochemistry & cell biology 2018-09, Vol.102, p.101-108 |
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Sprache: | eng |
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Zusammenfassung: | The role of caspase-2 in cell death regulation remains largely unknown. In this study we have analyzed the involvement of caspase-2 in RIPK1-regulated necrosis (necroptosis) in human ovarian carcinoma cells. We show that these cells undergo necroptosis upon treatment with the DNA damaging drug cisplatin in combination with the pan-caspase inhibitor zVAD-fmk. Downregulation of caspase-2 leads to an increase of necroptosis in CAOV-4 cells. Interestingly, an association of caspase-2 to the necrosome complex was not detected. Importantly, downregulation of caspase-2 with shRNA or CRISPR/Cas9 system led to an enhanced phosphorylation of RIPK1 and MLKL. Taken together, our data strongly indicate that caspase-2 negatively regulates necroptotic cell death, which might play an important role in further therapeutic applications. |
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ISSN: | 1357-2725 1878-5875 1878-5875 |
DOI: | 10.1016/j.biocel.2018.07.006 |