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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
Published on: August 7, 2018
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Is SIRT2 required for necroptosis?
Kim Newton1, Joanne M Hildebrand2, Zhirong Shen3
1Genentech, Inc., South San Francisco, California 94080, USA.
Nature
|February 28, 2014
Summary
This study investigated the role of SIRT2 in necroptosis, a form of programmed cell death. Researchers found that inhibiting or removing SIRT2 did not protect cells from necroptosis, questioning its importance in this pathway.
Area of Science:
- Cellular biology
- Molecular mechanisms of cell death
Background:
- Sirtuins, a class of proteins, regulate cellular processes through deacetylation.
- Previous research suggested SIRT2 is essential for necroptosis, a regulated cell death pathway.
Purpose of the Study:
- To confirm and investigate the role of SIRT2 in necroptosis.
- To challenge the existing hypothesis on SIRT2's requirement for necroptosis.
Main Methods:
- Utilized multiple SIRT2 inhibitors (AGK2) and gene silencing techniques (siRNAs).
- Employed knockout mouse models (Sirt2-/-) and wild-type controls.
- Assessed cell death in response to tumor necrosis factor (TNF) and Systemic Inflammatory Response Syndrome (SIRS) induction.
Main Results:
- Inhibition or depletion of SIRT2 did not confer protection against necroptosis.
- Sirt2-/- mice exhibited increased susceptibility to TNF-induced SIRS compared to wild-type mice.
- Mice deficient in Ripk3 (Ripk3-/-) were resistant to necroptosis, serving as a positive control.
Conclusions:
- The findings challenge the established role of SIRT2 in the necroptosis pathway.
- SIRT2 may not be a critical regulator of necroptosis as previously suggested.
- Further investigation is needed to fully elucidate SIRT2's function in cell death.
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