Is SIRT2 required for necroptosis?
Publication Year 2014-02-27,Volume 506,Issue #7489,Page E4-6
Journal Title
Publication Type
Journal Article
Sirtuins can promote deacetylation of a wide range of substrates in diverse cellular compartments to regulate many cellular processes1, 2; recently, Narayan et al.3 reported that SIRT2 was required for necroptosis on the basis of their findings that SIRT2 inhibition, knockdown or knockout prevented necroptosis. We sought to confirm and explore the role of SIRT2 in necroptosis and tested four different sources of the SIRT2 inhibitor AGK2, three independent short interfering RNAs (siRNAs) against Sirt2, and cells from two independently generated Sirt2−/− mouse strains; however, we were unable to show that inhibiting or depleting SIRT2 protected cells from necroptosis. Furthermore, Sirt2−/− mice succumbed to tumour-necrosis factor (TNF)-induced systemic inflammatory response syndrome (SIRS) more rapidly than wild-type mice, whereas Ripk3−/− mice were resistant. Our results therefore question the importance of SIRT2 in the necroptosis cell death pathway
WEHI Research Division(s)
Molecular Genetics Of Cancer; Cell Signalling And Cell Death
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Creation Date: 2014-03-19 09:37:27
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