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Sirtuin 5 Is Regulated by the SCFCyclin F Ubiquitin Ligase and Is Involved in Cell Cycle Control.
Christine A Mills1, Xianxi Wang2, Dhaval P Bhatt1
1Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Molecular and Cellular Biology
|November 10, 2020
Summary
Scientists discovered that cyclin F targets sirtuin 5 (SIRT5) for degradation, impacting cell cycle progression. This finding links metabolic enzyme SIRT5 to cell cycle regulation and metabolism.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The ubiquitin-proteasome system regulates cell cycle progression.
- Cyclin F is an F-box protein within SCF E3 ubiquitin ligase complexes.
- Identifying substrates of SCFCyclin F complexes has been challenging.
Purpose of the Study:
- To identify novel substrates of the SCFCyclin F complex.
- To investigate the role of sirtuin 5 (SIRT5) in cell cycle regulation.
Main Methods:
- Genetic screening using yeast mutants.
- Co-immunoprecipitation to confirm protein interactions.
- Western blotting to assess protein ubiquitination, abundance, and stability.
- Flow cytometry to analyze cell cycle distribution.
- Global proteomic analysis to identify signaling pathway changes.
Main Results:
- Sirtuin 5 (SIRT5) was identified as a novel substrate of cyclin F.
- Cyclin F interacts with SIRT5, promoting its ubiquitination and reducing its stability.
- SIRT5 knockout leads to cell cycle arrest in G1 phase with increased S and G2/M populations.
- Proteomic analysis revealed altered cyclin-dependent kinase (CDK) signaling in SIRT5 knockout cells.
Conclusions:
- SIRT5 is a novel substrate regulated by cyclin F, linking metabolic processes to cell cycle control.
- Cyclin F-mediated regulation of SIRT5 influences cell cycle progression.
- These findings suggest a functional connection between SIRT5, cell cycle regulation, and cellular metabolism.
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