Scher Michael B, Vaquero Alejandro, Reinberg Danny
Howard Hughes Medical Institute, New York University Medical School, New York, New York 10016, USA.
Genes Dev. 2007 Apr 15;21(8):920-8. doi: 10.1101/gad.1527307.
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 approximately 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.
在人类中，至少有七种类Sir2蛋白（SirT1 - 7），它们具有多种功能，包括对染色质结构和代谢的调节。已表明SirT3水平与延长寿命相关，定位于线粒体，并在棕色脂肪组织中高度表达。在人类中，SirT3以两种形式存在，一种是约44 kDa的全长蛋白，另一种是在其N端缺少142个氨基酸的加工多肽。我们发现，在正常细胞生长条件下，SirT3不仅定位于线粒体，还定位于细胞核。SirT3的全长和加工形式在体外均靶向H4 - K16进行去乙酰化，并且当被招募到一个基因时，在体内也能使H4 - K16去乙酰化。使用针对SirT3 N端的高度特异性抗体，我们发现，在细胞应激时，SirT3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SirT3自身的过表达。
