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Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
Caspase-mediated changes in Sir2alpha during apoptosis.
Shizue Ohsawa1, Masayuki Miura
1Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
FEBS Letters
|October 10, 2006
Summary
Mammalian Sir2alpha, a protein involved in aging and stress response, is cleaved by caspases during apoptosis. This cleavage causes Sir2alpha to move from the nucleus to the cytoplasm, indicating its role in programmed cell death.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Silent information regulator 2 (Sir2) is an NAD(+)-dependent deacetylase regulating chromatin and lifespan.
- Mammalian Sir2alpha homologue is implicated in protection against stress-induced apoptosis.
Purpose of the Study:
- To investigate the role and modifications of mammalian Sir2alpha during apoptosis.
Main Methods:
- Analysis of Sir2alpha cleavage by caspases.
- Observation of Sir2alpha subcellular localization during apoptosis.
- Inhibition studies using caspase-9 dominant-negative mutant and Bcl-xL.
Main Results:
- Mammalian Sir2alpha is directly cleaved by initiator and executioner caspases.
- Apoptotic cells show Sir2alpha relocation from the nucleus to the cytoplasm.
- Caspase-9 inhibition and Bcl-xL significantly reduced Sir2alpha alterations.
Conclusions:
- Mammalian Sir2alpha undergoes caspase-dependent dynamic changes during apoptosis.
- These modifications suggest a role for Sir2alpha in the apoptotic pathway.
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