A high-confidence interaction map identifies SIRT1 as a mediator of acetylation of USP22 and the SAGA coactivator complex.
Although many functions and targets have been attributed to the histone and protein deacetylase SIRT1, a comprehensive analysis of SIRT1 binding proteins yielding a high-confidence interaction map has not been established. Using a comparative statistical analysis of binding partners, we have assembled a high-confidence SIRT1 interactome. Employing this method, we identified the deubiquitinating enzyme ubiquitin-specific protease 22 (USP22), a component of the deubiquitinating module (DUBm) of the SAGA transcriptional coactivating complex, as a SIRT1-interacting partner. We found that this interaction is highly specific, requires the ZnF-UBP domain of USP22, and is disrupted by the inactivating H363Y mutation within SIRT1. Moreover, we show that USP22 is acetylated on multiple lysine residues and that alteration of a single lysine (K129) within the ZnF-UBP domain is sufficient to alter interaction of the DUBm with the core SAGA complex. Furthermore, USP22-mediated recruitment of SIRT1 activity promotes the deacetylation of individual SAGA complex components. Our results indicate an important role of SIRT1-mediated deacetylation in regulating the formation of DUBm subcomplexes within the larger SAGA complex.
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GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-N GENE-N GENE-Y GENE-N GENE-Y CHEMICAL GENE-Y GENE-N GENE-N GENE-N GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-N CHEMICAL CHEMICAL GENE-N GENE-Y GENE-N GENE-N GENE-Y
SIRT1 ubiquitin-specific protease 22 USP22 SAGA SIRT1 ZnF-UBP domain histone USP22 H363Y SIRT1 ZnF USP22 protein deacetylase ZnF-UBP domain DUBm SAGA SIRT1 USP22 SIRT1 SIRT1 USP22 lysine SAGA lysine ZnF SAGA SIRT1 DUBm SAGA SIRT1