| First Author | Sobuz SU | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Cell Res | Volume | 1866 |
| Issue | 9 | Pages | 1355-1367 |
| PubMed ID | 31075303 | Mgi Jnum | J:277821 |
| Mgi Id | MGI:6323967 | Doi | 10.1016/j.bbamcr.2019.05.001 |
| Citation | Sobuz SU, et al. (2019) SIRT7 regulates the nuclear export of NF-kappaB p65 by deacetylating Ran. Biochim Biophys Acta Mol Cell Res 1866(9):1355-1367 |
| abstractText | Sirtuin 7 (SIRT7) is an NAD(+)-dependent lysine deacetylase that regulates diverse biological processes. We recently observed that SIRT7 deficiency suppresses the nuclear accumulation of p65, which is a component of nuclear factor kappa B. However, the underlying molecular mechanism remains elusive. In this study, we demonstrated that SIRT7 interacts with a small GTPase, Ras-related nuclear antigen (Ran), and deacetylates Ran at K37. The nuclear export of p65 was facilitated in SIRT7-deficient fibroblast cells, while the nuclear export was inhibited in SIRT7-deficient cells expressing K37R-Ran (deacetylation-mimicking mutant). Additionally, the nuclear export of p65 in wild-type fibroblast cells was promoted by K37Q-Ran (acetylation-mimicking mutant). K37Q-Ran exhibited an increased ability to bind to chromosome region maintenance 1 (CRM1), which is a major nuclear receptor that mediates the export of cargo proteins, and enhanced the binding between p65 and CRM1. These data suggest that SIRT7 is a lysine deacetylase that targets the K37 residue of Ran to suppress the nuclear export of p65. |
