Phospho-Topoisomerase IIα (Ser1469) (D4F5) Rabbit mAb

• 产品编号：CST-13072S      品牌：CST       原厂货号：13072S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Topoisomerase IIα (Ser1469) (D4F5) Rabbit mAb 能够检测内源性Ser1469位点磷酸化的topoisomerase IIα总蛋白。该单克隆抗体是采用合成的与人源topoisomerase IIα 蛋白的Ser1469残基周围序列相对应的肽段免疫动物而生产的。DNA拓扑异构酶I和II是核酶，并且type II是由两个高度同源的异构体：拓扑异构酶 IIα 和IIβ。这些酶可调控DNA的拓扑结构、维持基因组完整性，并且对于如DNA复制、重组、转录和染色体分离等通过DNA双链穿越彼此而实现的过程是必需的(1)。拓扑异构酶I能使双螺旋DNA的一条单链产生切刻并重新结合，而拓扑异构酶 II可使双链DNA瞬时断裂和关闭 (2)。拓扑异构酶对不同应激是非常敏感的。酸性PH或氧化应激能使拓扑异构酶转变为DNA断裂核酸酶，从而引起基因组的不稳定性和细胞死亡。 DNA损伤拓扑异构酶靶点药物(e.g. etoposide)也能将拓扑异构酶转变成核酸酶，并且该酶通常被诱捕作为中间物，共价地结合到剪切的DNA链的5+末端。研究发现该中间物能导致基因组的不稳定性和细胞死亡，因此那些靶定拓扑异构酶的药剂是癌症化疗药物之后备受追捧的(3)。Ca2+调节拓扑异构酶 IIa Ser1106位点的磷酸化可调节该酶的活性和对靶药物的敏感性(4)。Casein kinase 2 (CK2)在Ser1469位点磷酸化DNA topoisomerase IIα以产生一个能够被有丝分裂特异性抗体MPM-2识别的位点 (5)。

1. Wang, J.C. (2002) Nat. Rev. Mol. Cell. Biol. 3, 430-440.
2. Pulleyblank, .E. (1997) Science 277, 648-649.
3. Li, T.K. and Liu, L.F. (2001) Annu. Rev. Pharmacol. Toxicol. 41, 53-77.
4. Chikamori, K. et al. (2003) J. Biol. Chem. 278, 12696-12702.
5. Escargueil, A.E. et al. (2000) J Biol Chem 275, 34710-8.

原厂资料：

Specificity / Sensitivity

Phospho-Topoisomerase IIα (Ser1469) (D4F5) Rabbit mAb recognizes endogenous levels of topoisomerase IIα protein only when phosphorylated at Ser1469.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser1469 of human topoisomerase IIα protein.

Background

DNA topoisomerases I and II are nuclear enzymes; type II consists of two highly homologous isoforms: topoisomerase IIα and IIβ. These enzymes regulate the topology of DNA, maintain genomic integrity, and are essential for processes such as DNA replication, recombination, transcription, and chromosome segregation by allowing DNA strands to pass through each other (1). Topoisomerase I nicks and rejoins one strand of the duplex DNA, while topoisomerase II transiently breaks and closes double-stranded DNA (2). Topoisomerases are very susceptible to various stresses. Acidic pH or oxidative stress can convert topoisomerases to DNA-breaking nucleases, causing genomic instability and cell death. DNA-damaging topoisomerase targeting drugs (e.g., etoposide) also convert topoisomerases to nucleases, with the enzyme usually trapped as an intermediate that is covalently bound to the 5+ end of the cleaved DNA strand(s). Research studies have shown that this intermediate leads to genomic instability and cell death. Thus, agents that target topoisomerases are highly sought after cancer chemotherapeutic drugs (3). Ca²⁺-regulated phosphorylation of topoisomerase IIα at Ser1106 modulates the activity of this enzyme and its sensitivity to targeting drugs (4).Casein kinase 2 (CK2) phosphorylates DNA topoisomerase IIα on Ser1469 to generate a site recognized by the mitosis-specific antibody MPM-2 (5).

1. Wang, J.C. (2002) Nat. Rev. Mol. Cell. Biol. 3, 430-440.
2. Pulleyblank, .E. (1997) Science 277, 648-649.
3. Li, T.K. and Liu, L.F. (2001) Annu. Rev. Pharmacol. Toxicol. 41, 53-77.
4. Chikamori, K. et al. (2003) J. Biol. Chem. 278, 12696-12702.
5. Escargueil, A.E. et al. (2000) J Biol Chem 275, 34710-8.

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