SirT7 (D3K5A) Rabbit mAb

• 产品编号：CST-5360S      品牌：CST       原厂货号：5360S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

SirT7 （D3K5A）Rabbit mAb 兔单抗能够检测内源性的SirT7总蛋白水平。该抗体不会与其他sirtuin蛋白发生交叉反应。该单克隆抗体是由针对人SirT7蛋白氨基端的重组蛋白免疫动物而生产的。沉默信息调节因子（SIR2）基因家族是一类高度保守的基因，能够编码烟酰胺腺嘌呤二核苷酸（NAD）依赖性的去乙酰化酶，亦称III类组蛋白去乙酰化酶。在这些基因中，酿酒酵母Sir2是最早被发现，并且了解得最清楚的。Sir2 参与了交配型基因座的沉默，端粒维持，DNA损伤应答和细胞衰老(1)。SirT7，是Sir2在哺乳动物中的同源基因，主要分布在核仁，在造血细胞尤其是骨髓祖细胞中有显著表达。SirT7可以在序列特异性DNA结合转录因子如Elk-4的作用下，募集到染色体上并发挥功能，将启动子上的组蛋白H3 Lys18位点的乙酰基脱掉，以促进转录抑制（3）。有趣的是，SirT7的过表达会导致组蛋白H3 Lys18位点乙酰化水平的全面下降。根据研究文献，此种表型与前列腺癌、肺癌、肾癌以及胰腺癌预后差都有关联（3-5）。此外，有研究表明， 一些癌细胞转化表型的维持需要SirT7的参与，其中包括锚定非依赖性细胞生长，低血清条件细胞生长以及异种移植试验中肿瘤形成（3）。SirT7同样也参与了E1A 导致的组蛋白H3 Lys18位点乙酰化水平的下降，SirT7同样参与了E1A导致的组蛋白H3 Lys18位点乙酰化水平的下降，诱导细胞进入细胞周期以及逃脱接触抑制（3）的过程。总而言之，这些研究结果都强烈表明SirT7是细胞转化的重要调控因子。研究表明 SirT7 基因位于染色体 17q25.3，此区域在急性白血病和淋巴瘤（2）中会频繁的发生改变，并且已经在多种类型的癌症（6-8）中检测到SirT7的过表达和扩增。

1. Guarente, L. (1999) Nat Genet 23, 281-5.
2. Voelter-Mahlknecht, S. et al. (2006) Int J Oncol 28, 899-908.
3. Barber, M.F. et al. (2012) Nature 487, 114-8.
4. Manuyakorn, A. et al. (2010) J Clin Oncol 28, 1358-65.
5. Seligson, D.B. et al. (2009) Am J Pathol 174, 1619-28.
6. Ashraf, N. et al. (2006) Br J Cancer 95, 1056-61.
7. de Nigris, F. et al. (2002) Br J Cancer 86, 917-23.
8. Frye, R. (2002) Br J Cancer 87, 1479.

原厂资料：

Specificity / Sensitivity

SirT7 (D3K5A) Rabbit mAb recognizes endogenous levels of total SirT7 protein. This antibody does not cross-react with other sirtuin proteins.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a recombinant protein specific to the amino terminus of human SirT7 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). SirT7, a mammalian homolog of Sir2, is localized primarily in the nucleolus and is most prominently expressed in hematopoietic cells, especially myeloid progenitor cells (2). SirT7 is recruited to chromatin by sequence-specific DNA binding transcription factors such as Elk-4, where it functions to deacetylate Lys18 of histone H3 at gene promoters and facilitate transcriptional repression (3). Interestingly, overexpression of SirT7 induces a global decrease in histone H3 Lys18 acetylation levels, a phenotype that has been associated with poor prognosis in prostate, lung, kidney, and pancreatic cancers in the research literature (3-5). Furthermore, studies have also shown that SirT7 is required for the maintenance of several transformed phenotypes of cancer cells, including anchorage-independent cell growth, growth in low serum conditions, and tumor formation in xenograft assays (3). SirT7 is also required for the E1A-induced decrease in histone H3 Lys18 acetylation, induction of cell-cycle entry, and escape from contact inhibition (3). Taken together, these findings strongly suggest that SirT7 is an important regulator of cellular transformation. Research has shown that the SirT7 gene is located on chromosome 17q25.3, a region that is frequently altered in acute leukemia and lymphoma (2), and SirT7 overexpression and amplification have been detected in multiple types of cancer (6-8).

1. Guarente, L. (1999) Nat Genet 23, 281-5.
2. Voelter-Mahlknecht, S. et al. (2006) Int J Oncol 28, 899-908.
3. Barber, M.F. et al. (2012) Nature 487, 114-8.
4. Manuyakorn, A. et al. (2010) J Clin Oncol 28, 1358-65.
5. Seligson, D.B. et al. (2009) Am J Pathol 174, 1619-28.
6. Ashraf, N. et al. (2006) Br J Cancer 95, 1056-61.
7. de Nigris, F. et al. (2002) Br J Cancer 86, 917-23.
8. Frye, R. (2002) Br J Cancer 87, 1479.

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.