Phospho-BRCA1 (Ser1524) Antibody

• 产品编号：CST-9009S      品牌：CST       原厂货号：9009S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

磷酸化BRCA1（丝氨酸1524位）抗体能够检测内源性丝氨酸（1524位）磷酸化的BRCA1蛋白。该多克隆抗体是由合成的人源的针对BRCA1蛋白丝氨酸(1524位)磷酸化肽段免疫动物而生产的，利用A蛋白和多肽亲和层析方法纯化生产的。 乳腺癌易感性蛋白BRCA1和BRCA2在遗传性乳腺癌和卵巢癌中突变频率很高，而且在多种疾病相关过程中发挥作用，如DNA损伤修复、细胞周期进程、转录、泛素化和细胞凋亡(1-4)。Rad51定位到DNA双链断裂处(DSBs)需要BRCA2的参与，缺少BRCA1和BRCA2的细胞不能通过依赖Rad51的同源重组过程(HR)修复DSBs(5)。众多的DNA损伤诱导的BRCA1的磷酸化位点已被鉴定，包括丝氨酸988位，1189位，1387位，1423位，1457位，1524位和1542位。细胞周期依赖性的蛋白激酶激活包括Aurora A和CDK2，也可以分别在丝氨酸308位和1497位磷酸化BRCA1(6-10)。细胞周期依赖性的BRCA2丝氨酸3291位磷酸化被认为是关闭HR的机制，细胞在S期之后通过阻断羧基末端的Rad51结合位点来启动该机制(11)。在爪蟾中，ATR依赖和CLASPIN介导的BRCA1招募引起的丝氨酸1524位磷酸化响应DNA损伤.

1. Rahman, N. and Stratton, M.R. (1998) Annu Rev Genet 32, 95-121.
2. Gayther, S.A. et al. (1999) Am J Hum Genet 65, 1021-9.
3. Kerr, P. and Ashworth, A. (2001) Curr Biol 11, R668-76.
4. Scully, R. and Livingston, D.M. (2000) Nature 408, 429-32.
5. Tutt, A. and Ashworth, A. (2002) Trends Mol Med 8, 571-6.
6. Okada, S. and Ouchi, T. (2003) J Biol Chem 278, 2015-20.
7. Cortez, D. et al. (1999) Science 286, 1162-6.
8. Xu, B. et al. (2002) Cancer Res 62, 4588-91.
9. Ouchi, M. et al. (2004) J Biol Chem 279, 19643-8.
10. Ruffner, H. et al. (1999) Mol Cell Biol 19, 4843-54.
11. Esashi, F. et al. (2005) Nature 434, 598-604.
12. Lin, S. Y. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 6484-6489.

原厂资料：

Specificity / Sensitivity

Phospho-BRCA1 (Ser1524) Antibody detects endogenous levels of BRCA1 only when phosphorylated at Ser1524. 

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser1524 of human BRCA1. Antibodies are purified by protein A and peptide affinity chromatography. 

Background

The breast cancer susceptibility proteins BRCA1 and BRCA2 are frequently mutated in cases of hereditary breast and ovarian cancers and have roles in multiple processes related to DNA damage, repair, cell cycle progression, transcription, ubiquitination and apoptosis (1-4). BRCA2 has been shown to be required for localization of Rad51 to sites of double stranded breaks (DSBs) in DNA, and cells lacking BRCA1 and BRCA2 cannot repair DSBs through the Rad51-dependent process of homologous recombination (HR) (5). Numerous DNA-damage induced phosphorylation sites on BRCA1 have been identified, including serines 988, 1189, 1387, 1423, 1457, 1524 and 1542, and kinases activated in a cell cycle-dependent manner, including Aurora A and CDK2, can also phosphorylate BRCA1 at Ser308 and Ser1497, respectively (6-10). Cell cycle-dependent phosphorylation of BRCA2 at Ser3291 by CDKs has been proposed as a mechanism to switch off HR as cells progress beyond S-phase by blocking the carboxy-terminal Rad51 binding site (11). 

In Xenopus, in response to DNA damage, ATR-dependent and Claspin-mediated recruitment of BRCA1 leads to phosphorylation at Ser1524 (12).

1. Rahman, N. and Stratton, M.R. (1998) Annu Rev Genet 32, 95-121.
2. Gayther, S.A. et al. (1999) Am J Hum Genet 65, 1021-9.
3. Kerr, P. and Ashworth, A. (2001) Curr Biol 11, R668-76.
4. Scully, R. and Livingston, D.M. (2000) Nature 408, 429-32.
5. Tutt, A. and Ashworth, A. (2002) Trends Mol Med 8, 571-6.
6. Okada, S. and Ouchi, T. (2003) J Biol Chem 278, 2015-20.
7. Cortez, D. et al. (1999) Science 286, 1162-6.
8. Xu, B. et al. (2002) Cancer Res 62, 4588-91.
9. Ouchi, M. et al. (2004) J Biol Chem 279, 19643-8.
10. Ruffner, H. et al. (1999) Mol Cell Biol 19, 4843-54.
11. Esashi, F. et al. (2005) Nature 434, 598-604.
12. Lin, S. Y. et al. (2004) Proc. Natl. Acad. Sci. USA 101, 6484-6489.

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