SirT3 (D22A3) Rabbit mAb

• 产品编号：CST-5490S      品牌：CST       原厂货号：5490S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

SirT3 (D22A3) Rabbit mAb兔单抗能够检测内源性SirT3总蛋白水平。该抗体检测包括未剪切45 kDa大小的前体蛋白和剪切的28 kDa大小蛋白。通过合成的与鼠源SirT3蛋白Val130位点周围相应的多肽片段去免疫动物从而制备出此单克隆抗体。Silent Information Regulator (SIR2)家族基因是高度保守基因组，它们能编码烟酰胺腺呤二核苷酸依赖的蛋白去乙酰化酶，又称为组蛋白去乙酰化酶(histone deacetylase,HDAC)3。这些基因的最初发现和最好的特征是酿酒酵母( Saccharomyces cerevisiae)SIR2，它涉及交配型位点、端粒维持、DNA损伤反应和细胞老化的沉默(1)。SirT3是哺乳动物Sir2的直系同源物，它以两种形式存在人源细胞系中。全长44 kDa蛋白定位于细胞核，然而一个加工的28 kDa大小缺少142氨基酸残基蛋白只定位在线粒体中(2-4)。SirT3蛋白单一鼠类形式相当于加工的人源SirT3蛋白(2)。全长SirT3蛋白在线粒体基质中通过mitochondrial matrix processing peptidase (MMP)被加工(3)。SirT3蛋白的全长和加工的形式都具有酶促活性，并且在体外使组蛋白H3在Lys9位点和组蛋白H4在Lys16位点去乙酰化(2)。在线粒体中，SirT3也使acetyl-CoA synthetase 2 (AceCS2)的Lys642位点去乙酰化，并且激活AceCS2活性(5)。在多种生物中，限制热量摄入是与延长寿命有关联，并且在肥胖老鼠的白色和棕色脂肪中能增加SirT3表达，这认为SirT3蛋白在衰老中有一定作用(6)。两个实验证明指出SirT3蛋白调节线粒体的产热。首先，在棕色脂肪中暴露在低温下可增加SirT3表达，而增加温度可较少SirT3蛋白表达(6)。其次，SirT3的过表达导致mitochondrial uncoupling protein 1 (UCP1)蛋白水平增加(6)。SirT3蛋白水平也在某些乳腺癌组织中增加(7)。

1. Guarente, L. (1999) Nat Genet 23, 281-5.
2. Scher, M.B. et al. (2007) Genes Dev 21, 920-8.
3. Schwer, B. et al. (2002) J Cell Biol 158, 647-57.
4. Onyango, P. et al. (2002) Proc Natl Acad Sci USA 99, 13653-8.
5. Schwer, B. et al. (2006) Proc Natl Acad Sci USA 103, 10224-9.
6. Shi, T. et al. (2005) J Biol Chem 280, 13560-7.
7. Ashraf, N. et al. (2006) Br J Cancer 95, 1056-61.

原厂资料：

Specificity / Sensitivity

SirT3 (D22A3) Rabbit mAb detects endogenous levels of total SirT3 protein. This antibody recognizes both the uncleaved 45 kDa precursor protein and the cleaved 28 kDa processed protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val130 of mouse SirT3 protein.

Background

The Silent Information Regulator (SIR2) family of genes is a highly conserved group of genes that encode nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases, also known as Class III histone deacetylases. The first discovered and best characterized of these genes is Saccharomyces cerevisiae Sir2, which is involved in silencing of mating type loci, telomere maintenance, DNA damage response and cell aging (1). SirT3, a mammalian homolog of Sir2, exists in human cells in two forms. The full-length 44 kDa protein localizes to the nucleus, while a processed 28 kDa protein lacking 142 amino terminal residues localizes exclusively to the mitochondria (2-4). The single murine form of SirT3 is equivalent to the processed human SirT3 protein (2). Full-length SirT3 protein is processed in the mitochondrial matrix by the mitochondrial matrix processing peptidase (MMP) (3). Both full-length and processed forms of SirT3 are enzymatically active and de-acetylate histone H3 at Lys9 and histone H4 at Lys16 in vitro (2). SirT3 also de-acetylates Lys642 of acetyl-CoA synthetase 2 (AceCS2) and activates AceCS2 activity in the mitochondria (5). Restricted caloric intake, which is linked to increased lifespan in multiple organisms, increases SirT3 expression in white and brown adipocytes of obese mice, suggesting a role for SirT3 in aging (6). Two observations implicate SirT3 in the regulation of mitochondrial thermogenesis. First, exposure to cold temperatures increases SirT3 expression in brown adipocytes, while elevated temperatures reduce SirT3 expression (6). Second, over-expression of SirT3 results in increased levels of the mitochondrial uncoupling protein 1 (UCP1) (6). SirT3 protein levels are also elevated in certain breast cancers (7).

1. Guarente, L. (1999) Nat Genet 23, 281-5.
2. Scher, M.B. et al. (2007) Genes Dev 21, 920-8.
3. Schwer, B. et al. (2002) J Cell Biol 158, 647-57.
4. Onyango, P. et al. (2002) Proc Natl Acad Sci USA 99, 13653-8.
5. Schwer, B. et al. (2006) Proc Natl Acad Sci USA 103, 10224-9.
6. Shi, T. et al. (2005) J Biol Chem 280, 13560-7.
7. Ashraf, N. et al. (2006) Br J Cancer 95, 1056-61.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150
mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02%
sodium azide. Store at –20°C. Do not aliquot the antibody.