SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress
SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress
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DOI：
10.1101/gad.1527307
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发表时间：
2007-04-15
影响因子：
10.5
通讯作者：
Reinberg, Danny
中科院分区：
文献类型：
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作者：
Scher, Michael B.;Vaquero, Alejandro;Reinberg, Danny
在人类中，至少有七种Sir 2样蛋白（SirT 1 -7）具有不同的功能，包括调节染色质结构和代谢。SirT 3水平已被证明与延长的寿命相关，定位于线粒体，并在棕色脂肪组织中高度表达。在人类中，SirT 3以两种形式存在，一种类似于44 kDa的全长蛋白质和一种在其N末端缺少142个氨基酸的加工多肽。我们发现SirT 3不仅定位于线粒体，而且在正常细胞生长条件下定位于细胞核。全长和加工形式的SirT 3都靶向H4-K16进行体外脱乙酰化，并且当募集到基因中时可以在体内使H4-K16脱乙酰化。使用针对SirT 3的N末端的高度特异性抗体，我们发现SirT 3在细胞应激时从细胞核转运到线粒体。这包括依托泊苷和紫外线照射诱导的DNA损伤，以及SirT 3本身的过表达。
In humans, there are at least seven Sir2-like proteins (SirT1-7) with diverse functions, including the regulation of chromatin structure, and metabolism. SirT3 levels have been shown to correlate with extended life span, to localize to the mitochondria, and to be highly expressed in brown adipose tissue. In humans, SirT3 exists in two forms, a full-length protein of similar to 44 kDa and a processed polypeptide lacking 142 amino acids at its N terminus. We found that SirT3 not only localizes to the mitochondria, but also to the nucleus under normal cell growth conditions. Both the full-length and processed forms of SirT3 target H4-K16 for deacetylation in vitro and can deacetylate H4-K16 in vivo when recruited to a gene. Using a highly specific antibody against the N terminus of SirT3, we found that SirT3 is transported from the nucleus to the mitochondria upon cellular stress. This includes DNA damage induced by Etoposide and UV-irradiation, as well as overexpression of SirT3 itself.