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Is SIRT2 required for necroptosis?

Author

Listed:
  • Kim Newton

    (Genentech, Inc.)

  • Joanne M. Hildebrand

    (The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    University of Melbourne, Parkville, Victoria 3050, Australia)

  • Zhirong Shen

    (National Institute of Biological Sciences, Zhongguancun Life Science Park)

  • Diego Rodriguez

    (St Jude Children’s Research Hospital)

  • Silvia Alvarez-Diaz

    (The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    University of Melbourne, Parkville, Victoria 3050, Australia)

  • Sean Petersen

    (Genentech, Inc.)

  • Saumil Shah

    (Tufts University)

  • Debra L. Dugger

    (Genentech, Inc.)

  • Chunzi Huang

    (Emory Vaccine Center, Emory University School of Medicine)

  • Johan Auwerx

    (Laboratory of Integrative and Systems Physiology, EPFL, CH-1015 Lausanne, Switzerland)

  • Peter Vandenabeele

    (Molecular Signaling and Cell Death Unit, Inflammation Research Center, VIB, 9052 Gent, Belgium
    Ghent University, 9052 Gent, Belgium
    Methusalem BOF09/01M00709, Ghent University, 9052 Gent, Belgium)

  • Douglas R. Green

    (St Jude Children’s Research Hospital)

  • Avi Ashkenazi

    (Genentech, Inc.)

  • Vishva M. Dixit

    (Genentech, Inc.)

  • William J. Kaiser

    (Emory Vaccine Center, Emory University School of Medicine)

  • Andreas Strasser

    (The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    University of Melbourne, Parkville, Victoria 3050, Australia)

  • Alexei Degterev

    (Tufts University)

  • John Silke

    (The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
    University of Melbourne, Parkville, Victoria 3050, Australia)

Abstract

Arising from N. Narayan et al. Nature 492, 199–204 (2012)10.1038/nature11700 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.

Suggested Citation

  • 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., 2014. "Is SIRT2 required for necroptosis?," Nature, Nature, vol. 506(7489), pages 4-6, February.
    • Handle: RePEc:nat:nature:v:506:y:2014:i:7489:d:10.1038_nature13024
    DOI: 10.1038/nature13024
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