Journal article

Is SIRT2 required for necroptosis?

Kim Newton, Joanne M Hildebrand, Zhirong Shen, Diego Rodriguez, Silvia Alvarez-Diaz, Sean Petersen, Saumil Shah, Debra L Dugger, Chunzi Huang, Johan Auwerx, Peter Vandenabeele, Douglas R Green, Avi Ashkenazi, Vishva M Dixit, William J Kaiser, Andreas Strasser, Alexei Degterev, John Silke

NATURE | NATURE PUBLISHING GROUP | Published : 2014

Abstract

Sirtuins can promote deacetylation of a wide range of substrates in diverse cellular compartments and regulate many cellular processes¹,². Recently Narayan et al., reported that SIRT2 was required for necroptosis based on their findings that SIRT2 inhibition, knock-down or knock-out 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 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 TNF induced Syste..

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Awarded by NIH HHS