| First Author | Ghosh HS | Year | 2011 |
| Journal | Sci Rep | Volume | 1 |
| Pages | 150 | PubMed ID | 22355666 |
| Mgi Jnum | J:206118 | Mgi Id | MGI:5547906 |
| Doi | 10.1038/srep00150 | Citation | Ghosh HS, et al. (2011) SIRT1 associates with eIF2-alpha and regulates the cellular stress response. Sci Rep 1:150 |
| abstractText | SIRT1 is a NAD+ dependent protein deacetylase known to increase longevity in model organisms. SIRT1 regulates cellular response to oxidative and/or genotoxic stress by regulating proteins such as p53 and FOXO. The eukaryotic initiation factor-2, eIF2, plays a critical role in the integrated stress response pathway. Under cellular stress, phosphorylation of the alpha subunit of eIF2 is essential for immediate shut-off of translation and activation of stress response genes. Here we demonstrate that SIRT1 interacts with eIF2alpha. Loss of SIRT1 results in increased phosphorylation of eIF2alpha. However, the downstream stress induced signaling pathway is compromised in SIRT1-deficient cells, indicated by delayed expression of the downstream target genes CHOP and GADD34 and a slower post-stress translation recovery. Finally, SIRT1 co-immunoprecipitates with mediators of eIF2alpha dephosphorylation, GADD34 and CreP, suggesting a role for SIRT1 in the negative feedback regulation of eIF2alpha phosphorylation. |
