Identification of a Tissue-Restricted Isoform of SIRT1 Defines a Regulatory Domain that Encodes Specificity

• DOI: 10.1016/j.celrep.2017.03.012
• Publication Date: 2017-03-28T17:32:16Z
• Authors: Shaunak Deota; Tandrika Chattopa...; Deepti Ramachandran; Eric Armstrong; Beatriz Camacho; Babukrishna Maniy...; Amit Fulzele; Anne Gonzalez-de-...; John M. Denu; Ullas Kolthur-See...
• Keywords: Identification

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-ΔE2) that lacks exon 2 (E2). Candidate-based screening substrates demonstrated the domain encoded by key role specifying protein-protein interactions. E2 was both necessary sufficient for PGC1α binding, enhanced interaction with p53, thus downstream functions. Since SIRT1-FL SIRT1-ΔE2 were found to have similar intrinsic catalytic activities, propose tethers specific substrate proteins. Given absence liver, our findings provide insight into "metabolic functions" SIRT1-FL. Identification specificity will enhance understanding guide development therapeutic interventions.