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SIRT1 associates with eIF2-alpha and regulates the cellular stress response
Hiyaa Singhee Ghosh1, Boris Reizis, Paul D Robbins
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
Scientific Reports
|February 23, 2012
Summary
SIRT1 protein deacetylase interacts with eukaryotic initiation factor-2 alpha (eIF2α). Loss of SIRT1 impairs cellular stress response by increasing eIF2α phosphorylation and delaying gene expression.
Area of Science:
- Molecular Biology
- Cellular Stress Response
- Protein Deacetylation
Background:
- SIRT1, a NAD+-dependent protein deacetylase, influences longevity and stress response.
- The eukaryotic initiation factor-2 alpha (eIF2α) is crucial for the integrated stress response pathway.
- eIF2α phosphorylation controls translation shut-off and stress gene activation.
Purpose of the Study:
- To investigate the interaction between SIRT1 and eIF2α.
- To elucidate SIRT1's role in regulating eIF2α phosphorylation and downstream stress signaling.
- To understand SIRT1's contribution to cellular stress adaptation and translation recovery.
Main Methods:
- Co-immunoprecipitation assays to detect protein interactions.
- Western blotting to assess eIF2α phosphorylation levels.
- Quantitative PCR to measure stress-induced gene expression (CHOP, GADD34).
Main Results:
- SIRT1 directly interacts with eIF2α.
- SIRT1 deficiency leads to elevated eIF2α phosphorylation.
- SIRT1-deficient cells exhibit delayed CHOP and GADD34 expression and impaired translation recovery.
- SIRT1 co-immunoprecipitates with GADD34 and CreP, key eIF2α dephosphorylation mediators.
Conclusions:
- SIRT1 interacts with eIF2α and modulates its phosphorylation status.
- SIRT1 plays a critical role in the negative feedback regulation of eIF2α phosphorylation during cellular stress.
- SIRT1 is essential for efficient stress response gene activation and timely translation recovery.
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