Ubiquityl-Histone H2A (Lys119) (D27C4) XP? Rabbit mAb

• 产品编号：CST-8240P      品牌：Cell Signaling Technology       原厂货号：8240P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Ubiquityl-Histone H2A (Lys119) (D27C4) XP® Rabbit mAb兔单抗能够检测仅在Lys119位点泛素化的内源性histone H2A的蛋白水平。该抗体不能与其它泛素化的蛋白或游离的泛素发生交叉反应。通过合成的在Lys119单泛素化的人源histone H2A蛋白羧基端周围相应的多肽片段去免疫动物从而制备出单克隆抗体。核小体是由四种中心组蛋白(H2A、H2B、H3和H4)组成，它是染色质的主要构件模块。起初被认为是一个DNA包装的静态支架，目前组蛋白已经被认为是一个动态蛋白，其经历多种形式的翻译后修饰，包括乙酰化作用、磷酸化作用、甲基化作用和泛素化作用(1)。泛素是一个保守的76个氨基酸多肽单位，它通过泛素化过程共价连接许多细胞内蛋白。三个成分涉及蛋白质泛素化连接过程。泛素首先通过形成一个与活化元件E1一起的硫酯复合物被激活；随后活化的泛素转移到泛素载体蛋白E2，然后从E2传递到泛素连接酶E3的靶蛋白赖氨酸残基epsilon-NH2上(2)。Histone H2A通过Polycomb Repressor Complex 1 (PRC1)使Lys119位点单泛素化，并且对于发育的HOX基因的转录沉默和X染色体的失活起着关键作用(3-6)。PRC1是由Bmi1和RING1A (也称为RING1或RNF1)组成，两者都能提高催化亚单位RING1B (也称为RING2或RNF2)的E3泛素连接酶活性(3,4)。在DNA损伤的位点Histone H2A也使Lys119位点单泛素化。除了另外E3泛素连接酶RNF8之外，这个单泛素化过程需要PRC1成分Bmi1和RING1B，并且有助于随后的BRCA1复合物的招募，这主要通过RAP80/UIMC1(ubiquitin interactive motif containing 1 protein)的结合(7-10)。

1. Peterson, C.L. and Laniel, M.A. (2004) Curr Biol 14, R546-51.
2. Liu, F. and Walters, K.J. (2010) Trends Biochem Sci 35, 352-60.
3. Wang, H. et al. (2004) Nature 431, 873-8.
4. Cao, R. et al. (2005) Mol Cell 20, 845-54.
5. de Napoles, M. et al. (2004) Dev Cell 7, 663-76.
6. Fang, J. et al. (2004) J Biol Chem 279, 52812-5.
7. Ginjala, V. et al. (2011) Mol Cell Biol 31, 1972-82.
8. Bergink, S. et al. (2006) Genes Dev 20, 1343-52.
9. Marteijn, J.A. et al. (2009) J Cell Biol 186, 835-47.
10. Wu, J. et al. (2009) Mol Cell Biol 29, 849-60.

原厂资料：

Specificity / Sensitivity

Ubiquityl-Histone H2A (Lys119) (D27C4) XP® Rabbit mAb recognizes endogenous levels of histone H2A protein only when ubiquitinated at Lys119. The antibody does not cross-react with other ubiquitinated proteins or free ubiquitin.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human histone H2A protein in which Lys119 is mono-ubiquitinated.

Background

The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). Ubiquitin is a conserved 76 amino acid peptide unit that can be covalently linked to many cellular proteins by the ubiquitination process. Three components are involved in this protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thioester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (2). Histone H2A is mono-ubiquitinated at Lys119 by the Polycomb Repressor Complex 1 (PRC1) and is critical for transcriptional silencing of the developmental HOX genes and X chromosome inactivation (3-6). PRC1 is composed of Bmi1 and RING1A (also RING1 or RNF1), both of which act to enhance the E3 ubiquitin ligase activity of the catalytic subunit RING1B (also RING2 or RNF2) (3,4). Histone H2A is also mono-ubiquitinated at Lys119 at sites of DNA damage. This mono-ubiquitination event requires the PRC1 components Bmi1 and RING1B, in addition to another E3 ubiquitin ligase RNF8, and contributes to subsequent recruitment of the BRCA1 complex, via binding of RAP80/UIMC1 (ubiquitin interactive motif containing 1 protein) (7-10).

1. Peterson, C.L. and Laniel, M.A. (2004) Curr Biol 14, R546-51.
2. Liu, F. and Walters, K.J. (2010) Trends Biochem Sci 35, 352-60.
3. Wang, H. et al. (2004) Nature 431, 873-8.
4. Cao, R. et al. (2005) Mol Cell 20, 845-54.
5. de Napoles, M. et al. (2004) Dev Cell 7, 663-76.
6. Fang, J. et al. (2004) J Biol Chem 279, 52812-5.
7. Ginjala, V. et al. (2011) Mol Cell Biol 31, 1972-82.
8. Bergink, S. et al. (2006) Genes Dev 20, 1343-52.
9. Marteijn, J.A. et al. (2009) J Cell Biol 186, 835-47.
10. Wu, J. et al. (2009) Mol Cell Biol 29, 849-60.

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