| First Author | Deota S | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 13 | Pages | 3069-3077 |
| PubMed ID | 28355560 | Mgi Jnum | J:250995 |
| Mgi Id | MGI:6103602 | Doi | 10.1016/j.celrep.2017.03.012 |
| Citation | Deota S, et al. (2017) Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity. Cell Rep 18(13):3069-3077 |
| abstractText | The conserved NAD(+)-dependent deacylase SIRT1 plays pivotal, sometimes contrasting, roles in diverse physiological and pathophysiological conditions. In this study, we uncover a tissue-restricted isoform of SIRT1 (SIRT1-DeltaE2) that lacks exon 2 (E2). Candidate-based screening of SIRT1 substrates demonstrated that the domain encoded by this exon plays a key role in specifying SIRT1 protein-protein interactions. The E2 domain of SIRT1 was both necessary and sufficient for PGC1alpha binding, enhanced interaction with p53, and thus downstream functions. Since SIRT1-FL and SIRT1-DeltaE2 were found to have similar intrinsic catalytic activities, we propose that the E2 domain tethers specific substrate proteins. Given the absence of SIRT1-DeltaE2 in liver, our findings provide insight into the role of the E2 domain in specifying "metabolic functions" of SIRT1-FL. Identification of SIRT1-DeltaE2 and the conserved specificity domain will enhance our understanding of SIRT1 and guide the development of therapeutic interventions. |
