ARD1A Antibody

• 产品编号：CST-9046S      品牌：CST       原厂货号：9046S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

ARD1A抗体能够检测内源性的ARD1A总蛋白水平。该抗体不会与高同源性的ARD1B蛋白发生交叉反应。该抗体还能与未知来源的分子量为60kD的蛋白发生交叉反应。该多克隆抗体是用合成的与人源ARD1A蛋白Val171残基周围序列相对应的肽段免疫动物而生产的。该抗体通过蛋白A和多肽的亲和层析方式纯化获得。蛋白乙酰化修饰一种常见蛋白修饰，通常乙酰化修饰发生于蛋白的赖氨酸残基(ε残基乙酰化)和蛋白的N末端的多氨基酸残基(α残基乙酰化)。N端α乙酰转移酶ARD1的同源A蛋白（ARD1A,又称为NAA10)以及高同源性的N端ɑ乙酰转移酶ARD1的同源B蛋白（ARD1B,又称为NAA11或ARD2)是N末端乙酰转移酶复合物NatA的特有催化亚基（1-3）。该复合物由ARD1A或者ARD1B以及N端ɑ乙酰转移酶15(NAA15)辅助蛋白组成，位于核糖体上，在蛋白翻译过程起始甲硫氨酸裂解后乙酰化N端Ser-, Ala-, Gly-, Thr-, Cys-, Pro-, and Val（1-5）。N端ɑ乙酰化，与ε残基乙酰化功能类似，能够调控蛋白的稳定、活性、细胞定位以及蛋白相互作用(4,5)。ARD1A的缺失会引起N端乙酰转移酶的缺失(NATD)，严重影响生命体出生后生长(6)。除了作为NatA复合物中N端乙酰转移酶，单独的ARD1A和ARD1B蛋白能够将如HIF-1α, β-catenin, and AP-1 转录因子等多个目标蛋白的赖氨酸残基ε-氨基乙酰化，从而调控细胞的生长和分化(7-9)。在有氧条件下，由ARD1A介导的位于HIF-1ɑ的532位点的赖氨酸乙酰化，能够增强VHL的结合，从而增加HIF-1ɑ的泛素化和降解，下调HIF-1ɑ的目标基因，参与血管生成、细胞凋亡和葡萄糖代谢(7)。在缺氧条件下，降低ARD1A的表达，有助于稳定的HIF-1ɑ蛋白以及上调HIF-1ɑ的靶基因(7) 。另外，ARD能够乙酰化和激活β-catenin和AP-1转录因子，导致细胞周期蛋白D1的表达从而促进细胞增殖和肿瘤发生(8,9)。有趣的是，ARD1A的乙酰转移酶活性是由其自身136位点赖氨酸自我乙酰化进行调控的，自我乙酰化ARD1A能够促进细胞增殖和肿瘤发生(9)。调查研究表明ARD1在多种癌症中过表达，包括乳腺癌，前列腺癌，肺癌，大肠癌（10-13）。

1. Arnesen, T. et al. (2005) Biochem J 386, 433-43.
2. Arnesen, T. et al. (2006) BMC Biochem 7, 13.
3. Pang, A.L. et al. (2009) Biol Reprod 81, 302-9.
4. Van Damme, P. et al. (2011) FEBS J 278, 3822-34.
5. Polevoda, B. and Sherman, F. (2000) J Biol Chem 275, 36479-82.
6. Rope, A.F. et al. (2011) Am J Hum Genet 89, 28-43.
7. Jeong, J.W. et al. (2002) Cell 111, 709-20.
8. Lim, J.H. et al. (2006) Cancer Res 66, 10677-82.
9. Seo, J.H. et al. (2010) Cancer Res 70, 4422-32.
10. Arnesen, T. et al. (2005) Thyroid 15, 1131-6.
11. Ren, T. et al. (2008) Cancer Lett 264, 83-92.
12. Yu, M. et al. (2009) Oncol Rep 21, 909-15.
13. Yu, M. et al. (2009) Cancer Invest 27, 978-83.

原厂资料：

Specificity / Sensitivity

ARD1A Antibody recognizes endogenous levels of total ARD1A protein. This antibody does not cross-react with the highly homologous ARD1B protein. This antibody also cross-reacts with a protein of unknown origin at 60 kDa.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val171 of human ARD1A protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Protein acetylation is a common modification that occurs both at lysine residues within proteins (ε-amino acetylation) and multiple amino acid residues at the N-terminus of proteins (α-amino acetylation). The N-α-acetyltransferase ARD1 homolog A protein (ARD1A, also known as NAA10) and the highly homologous N-α-acetyltransferase ARD1 homolog B protein (ARD1B, also known as ARD2 or NAA11) are mutually exclusive catalytic subunits of the N-terminal acetyltransferase complex (NatA) (1-3). This complex, which consists of either ARD1A or ARD1B and the N-α-acetyltransferase 15 (NAA15) auxiliary protein, localizes to ribosomes where it functions to acetylate Ser-, Ala-, Gly-, Thr-, Cys-, Pro-, and Val- N-termini after initiator methionine cleavage during protein translation (1-5). Like ε-amino acetylation, N-terminal α-amino acetylation functions to regulate protein stability, activity, cellular localization, and protein-protein interactions (4,5). Defects in ARD1A have been shown to cause N-terminal acetyltransferase deficiency (NATD), which results in severe delays and defects in postnatal growth (6). 
 
 In addition to functioning as N-terminal acetyltransferases in the NatA complex, free ARD1A and ARD1B proteins regulate cell growth and differentiation through ε-amino acetylation of lysine residues in multiple target proteins, including the HIF-1α, β-catenin, and AP-1 transcription factors (7-9). ARD1A-mediated acetylation of HIF-1α at Lys532 under normoxic conditions enhances binding of VHL, leading to increased ubiquitination and degradation of HIF-1α and down-regulation of HIF-1α target genes involved in angiogenesis, apoptosis, cellular proliferation, and glucose metabolism (7). Decreased expression of ARD1A under hypoxic conditions contributes to the stabilization of HIF-1α and upregulation of target genes (7). ARD1A also promotes cell proliferation and tumorigenesis by acetylating and activating β-catenin and AP-1 transcription factors, leading to the stimulation of cyclin D1 expression (8,9). Interestingly, the acetyltransferase activity of ARD1A is regulated by autoacetylation at Lys136, which is required for the ability of ARD1A to promote proliferation and tumorigenesis (9). Research studies have shown that ARD1 proteins are over-expressed in multiple cancers, including breast, prostate, lung, and colorectal cancers (10-13).

1. Arnesen, T. et al. (2005) Biochem J 386, 433-43.
2. Arnesen, T. et al. (2006) BMC Biochem 7, 13.
3. Pang, A.L. et al. (2009) Biol Reprod 81, 302-9.
4. Van Damme, P. et al. (2011) FEBS J 278, 3822-34.
5. Polevoda, B. and Sherman, F. (2000) J Biol Chem 275, 36479-82.
6. Rope, A.F. et al. (2011) Am J Hum Genet 89, 28-43.
7. Jeong, J.W. et al. (2002) Cell 111, 709-20.
8. Lim, J.H. et al. (2006) Cancer Res 66, 10677-82.
9. Seo, J.H. et al. (2010) Cancer Res 70, 4422-32.
10. Arnesen, T. et al. (2005) Thyroid 15, 1131-6.
11. Ren, T. et al. (2008) Cancer Lett 264, 83-92.
12. Yu, M. et al. (2009) Oncol Rep 21, 909-15.
13. Yu, M. et al. (2009) Cancer Invest 27, 978-83.

注意事项：

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