Caspase-2 is a negative regulator of necroptosis

The International Journal of Biochemistry & Cell Biology
Alexey V ZamaraevI N Lavrik

Abstract

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.

Citations

Nov 24, 2019·Bulletin of Experimental Biology and Medicine·A V ZamaraevG S Kopeina
Nov 14, 2019·Cell Death & Disease·Tamás MolnárGábor Koncz
Nov 5, 2019·Frontiers in Immunology·Valéria Bumiller-BiniAngelica Beate Winter Boldt
Oct 5, 2020·Cell Death & Disease·Alexey V ZamaraevGelina S Kopeina
Mar 24, 2021·Trends in Cell Biology·Gelina S Kopeina, Boris Zhivotovsky
Jul 7, 2021·Cell Death Discovery·Elena V SazonovaBoris Zhivotovsky

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