期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1866, 期 9, 页码 1355-1367出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2019.05.001
关键词
SIRT7; Deacetylation; Nuclear export; Nuclear factor kappa B (NF-kappa B); p65; Inhibitor of NF-kappa B (I kappa B); Exportin; Nuclear export
资金
- JSPS KAKENHI [16H05328, 19H03711]
- AMED [JP18gm5010002]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [19H03711, 16H05328] Funding Source: KAKEN
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.
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