Phospho-CDC20 (Ser51) Antibody

• 产品编号：CST-8038S      品牌：CST       原厂货号：8038S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-CDC20 (Ser51) Antibody 能够识别内源性丝氨酸（51位）磷酸化的CDC20蛋白。该多克隆抗体是由合成的人源的针对CDC20蛋白丝氨酸(51位)磷酸化肽段免疫动物，利用A蛋白和多肽亲和层析方法纯化生产的。细胞分裂周期的维持需要准确避免基因损伤的累积。这一过程由真核细胞中普遍存在的所谓检验点分子环路控制(1)。在G1/S和G2/M转换期，检验点先于复制和分化分别监控DNA完整性和细胞生长。cdc2-cyclin B激酶是调节G2/M过渡的重要激酶(2,3)。Cdc2的苏氨酸14位和酪氨酸15位在G2期可被Wee1和Myt1两个激酶磷酸化，从而失活。肿瘤抑制蛋白视网膜母细胞瘤蛋白(Rb)通过G1末期检验点控制细胞进程，是G1/S 转换的重要调节子(4)。在G1期的早中期， Rb蛋白与转录因子E2F结合并抑制其表达(5)。G1期晚期，CDKs磷酸化Rb诱导其与E2F解离，S期促进基因得以转录。在体外，Rb可以被cdc2, cdk2, and cdk4/6进行多位点磷酸化 (6-8)。DNA损伤可以触发G2/M及G1/S检验点。DNA损伤能够激活DNA-PK/ATM/ATR激酶，后者能够使Chk丝氨酸345位 (9)，Chk2苏氨酸68位和p53发生磷酸化(11)。Chk激酶通过丝氨酸216位失活cdc25，从而阻断cdc2的激活。在细胞周期的有丝分裂期和G1期，CDC20结合并激活后期促进复合物（APC）（12)。并且，CDC20对于APC/cyclosome（APC/C）复合物中泛素连接酶的活性是必须的。有丝分裂中期，MAD2L1使CDC20-APC/C复合物失活，但在后期，这种抑制作用消失，CDC20-APC/C能够降解其底物(13)。p53 和p21可以抑制由基因毒性应激引起的CDC20表达和p53的异常表达。肿瘤细胞中，siRNA介导的CDC20水平下调可导致细胞生长减缓并诱导G(2)/M期阻滞，提示CDC20是肿瘤治疗的一个可能的靶蛋白(14)。神经元回路的形成需要突触前轴突分化和突触形成。CDC20-APC 通过触发转录因子NeuroD2的降解调节有丝分裂后神经元的突触前分化(15)。CAMKIIβ对CDC20丝氨酸51位的磷酸化使CDC20与中心小体分离。结果，CDC20-APC复合体的活性被抑制，原代神经元树突发生从生长到回缩的转变(16)。

1. Nurse, P. (1997) Cell 91, 865-7.
2. Norbury, C. and Nurse, P. (1992) Annu Rev Biochem 61, 441-70.
3. Watanabe, N. et al. (1995) EMBO J 14, 1878-91.
4. Sherr, C.J. (1996) Science 274, 1672-7.
5. Dyson, N. (1998) Genes Dev 12, 2245-62.
6. Kitagawa, M. et al. (1996) EMBO J 15, 7060-9.
7. Lundberg, A.S. and Weinberg, R.A. (1998) Mol Cell Biol 18, 753-61.
8. Harbour, J.W. et al. (1999) Cell 98, 859-69.
9. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
10. Matsuoka, S. et al. (2000) Proc Natl Acad Sci USA 97, 10389-94.
11. Tibbetts, R.S. et al. (1999) Genes Dev 13, 152-7.
12. Fang, G. et al. (1998) Mol Cell 2, 163-71.
13. Fang, G. et al. (1998) Genes Dev 12, 1871-83.
14. Kidokoro, T. et al. (2008) Oncogene 27, 1562-71.
15. Yang, Y. et al. (2009) Science 326, 575-8.
16. Puram, S.V. et al. (2011) Nat Neurosci , .

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Rat

Specificity / Sensitivity

Phospho-CDC20 (Ser51) Antibody recognizes endogenous levels of CDC20 protein only when phosphorylated at Ser51. 

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Ser51 of human CDC20 protein. Antibodies are purified by protein A and peptide affinity chromatography. 

Background

The cell division cycle demands accuracy to avoid the accumulation of genetic damage. This process is controlled by molecular circuits called "checkpoints" that are common to all eukaryotic cells (1). Checkpoints monitor DNA integrity and cell growth prior to replication and division at the G1/S and G2/M transitions, respectively. The cdc2-cyclin B kinase is pivotal in regulating the G2/M transition (2,3). Cdc2 is phosphorylated at Thr14 and Tyr15 during G2-phase by the kinases Wee1 and Myt1, rendering it inactive. The tumor suppressor protein retinoblastoma (Rb) controls progression through the late G1 restriction point (R) and is a major regulator of the G1/S transition (4). During early and mid G1-phase, Rb binds to and represses the transcription factor E2F (5). The phosphorylation of Rb late in G1-phase by CDKs induces Rb to dissociate from E2F, permitting the transcription of S-phase-promoting genes. In vitro, Rb can be phosphorylated at multiple sites by cdc2, cdk2, and cdk4/6 (6-8). DNA damage triggers both the G2/M and the G1/S checkpoints. DNA damage activates the DNA-PK/ATM/ATR kinases, which phosphorylate Chk at Ser345 (9), Chk2 at Thr68 (10) and p53 (11). The Chk kinases inactivate cdc25 via phosphorylation at Ser216, blocking the activation of cdc2. 

CDC20 binds to and activates the anaphase-promoting complex (APC) during mitosis and G1 phase of the cell cycle (12). Moreover, CDC20 is necessary for ubiquitin ligase activity of the APC/cyclosome (APC/C). In metaphase MAD2L1 inactivates the CDC20-APC/C complex, while in anaphase this inhibition is lost and CDC20-APC/C degrades its substrates (13). p53 and p21 suppress expression of CDC20 upon genotoxic stresses and ectopic introduction of p53. siRNA mediated knock-down of CDC20 in cancer cells leads to attenuated cell growth and induces G(2)/M arrest, suggesting that CDC20 is a possible therapeutic target of cancer (14). Organization of neuronal circuits requires presynaptic axonal differentiation and synapse formation. CDC20-APC regulates presynaptic differentiation in postmitotic neurons by triggering the required degradation of the transcription factor NeuroD2 (15). Phosphorylation of CDC20 at Ser51 by CAMKIIβ disperses CDC20 from the centrosome. As a result, CDC20-APC activity is inhibited and transition from growth to retraction of dendrites in primary neurons is triggered (16).

1. Nurse, P. (1997) Cell 91, 865-7.
2. Norbury, C. and Nurse, P. (1992) Annu Rev Biochem 61, 441-70.
3. Watanabe, N. et al. (1995) EMBO J 14, 1878-91.
4. Sherr, C.J. (1996) Science 274, 1672-7.
5. Dyson, N. (1998) Genes Dev 12, 2245-62.
6. Kitagawa, M. et al. (1996) EMBO J 15, 7060-9.
7. Lundberg, A.S. and Weinberg, R.A. (1998) Mol Cell Biol 18, 753-61.
8. Harbour, J.W. et al. (1999) Cell 98, 859-69.
9. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
10. Matsuoka, S. et al. (2000) Proc Natl Acad Sci USA 97, 10389-94.
11. Tibbetts, R.S. et al. (1999) Genes Dev 13, 152-7.
12. Fang, G. et al. (1998) Mol Cell 2, 163-71.
13. Fang, G. et al. (1998) Genes Dev 12, 1871-83.
14. Kidokoro, T. et al. (2008) Oncogene 27, 1562-71.
15. Yang, Y. et al. (2009) Science 326, 575-8.
16. Puram, S.V. et al. (2011) Nat Neurosci , .

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.