SIRT1 and SIRT3 Deacetylate Homologous Substrates
Author Information
Author(s): Hirschey Matthew D., Shimazu Tadahiro, Capra John A., Pollard Katherine S., Verdin Eric
Primary Institution: Gladstone Institute of Virology and Immunology, University of California, San Francisco
Hypothesis
Do SIRT1 and SIRT3 regulate homologous substrates in different cellular locations?
Conclusion
SIRT1 and SIRT3 deacetylate homologous substrates in the cytoplasm and mitochondria, respectively, suggesting an evolutionary relationship between these gene families.
Supporting Evidence
- SIRT1 deacetylates AceCS1 in the cytoplasm, while SIRT3 deacetylates AceCS2 in the mitochondria.
- HMGCS1 and HMGCS2 show high sequence similarity, indicating a conserved regulatory mechanism.
- Phylogenetic analysis suggests that the sirtuins and their substrates have an ancient evolutionary origin.
Takeaway
This study shows that two proteins, SIRT1 and SIRT3, help control similar processes in different parts of the cell, which might help us understand how they work together over time.
Methodology
The study involved phylogenetic analysis and experimental validation of substrate acetylation in HEK293 cells.
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