SIRT1 stabilizes PML promoting its sumoylation
SIRT1 stabilizes PML promoting its sumoylation
复制标题
DOI：
10.1038/cdd.2010.77
复制
发表时间：
2011-01-01
影响因子：
12.4
通讯作者：
Rivas, C.
中科院分区：
文献类型：
--
作者：
Campagna, M.;Herranz, D.;Rivas, C.
SIRT 1是与酵母Sir 2最接近的哺乳动物同源物，是一种NAD（+）依赖性脱乙酰酶，在癌症、衰老和代谢等过程中具有相关功能。SIRT 1具有弥散性核定位，但在PML上调后被募集到PML核体（PML-NB）。然而，SIRT 1在PML-NB中的功能尚不清楚。在这项研究中，我们发现缺乏SIRT 1的原代小鼠胚胎成纤维细胞含有减少的PML蛋白水平，在重新引入SIRT 1后增加。此外，HEK-293细胞中SIRT 1的过表达增加了PML蛋白的量，而SIRT 1的敲低降低了HeLa细胞中PML-NB的大小和数量以及PML蛋白的水平。SIRT 1在体外和体内以不依赖脱乙酰酶的方式刺激PML类小泛素化。重要的是，SIRT 1的缺乏减少了水泡性口炎病毒感染细胞的凋亡反应，并有利于这种PML敏感的病毒复制的程度。这些结果显示SIRT 1在PML和PML-NB控制中的新功能。Cell Death and Differentiation（2011）18，72-79; doi：10.1038/cdd.2010.77; 2010年6月25日在线发表
SIRT1, the closest mammalian homolog of yeast Sir2, is an NAD(+)-dependent deacetylase with relevant functions in cancer, aging, and metabolism among other processes. SIRT1 has a diffuse nuclear localization but is recruited to the PML nuclear bodies (PML-NBs) after PML upregulation. However, the functions of SIRT1 in the PML-NBs are unknown. In this study we show that primary mouse embryo fibroblasts lacking SIRT1 contain reduced PML protein levels that are increased after reintroduction of SIRT1. In addition, overexpression of SIRT1 in HEK-293 cells increases the amount of PML protein whereas knockdown of SIRT1 reduces the size and number of PML-NBs and the levels of PML protein in HeLa cells. SIRT1 stimulates PML sumoylation in vitro and in vivo in a deacetylase-independent manner. Importantly, the absence of SIRT1 reduces the apoptotic response of vesicular stomatitis virus-infected cells and favors the extent of this PML-sensitive virus replication. These results show a novel function of SIRT1 in the control of PML and PML-NBs. Cell Death and Differentiation (2011) 18, 72-79; doi: 10.1038/cdd.2010.77; published online 25 June 2010