Skp2 (D3G5) XP? Rabbit mAb

• 产品编号：CST-2652S      品牌：CST       原厂货号：2652S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Skp2 (D3G5) XP® Rabbit mAb兔单抗识别內源性的Skp2总蛋白。该抗体与Skp2α和Skp2β具有交叉反应性。该单克隆抗体经合成与人Skp2蛋白氨基末端邻近的氨基酸残基序列一致的肽段，免疫动物产生。F-box家族蛋白成员以大约40种氨基酸F-box模序而被命名为cyclin F(1,2)。F-box蛋白组成了Skp1-Cullin-F-box (SCF)泛素连接酶复合物的四个亚基中的一个。SCF复合物的底物特异性由可替换的F-box蛋白决定，其通过与磷酸化底物蛋白的结合并募集到SCF中心，从而发挥调节子的作用。F-box蛋白包括2种基本的结构域：F-box模序介导Skp1和一种富含亮氨酸重复序列的(LRR)结构域，从而介导底物的相互作用。S期激酶相关蛋白(Skp2)与cyclin A/CDK2相互作用，通过靶向细胞周期蛋白依赖激酶(CDK)抑制剂p27, p21, p130和泛素化作用以及随后的蛋白水解FoxO1转录因子，介导G1到S和G2到M期的转变(3-6)。Skp2蛋白在G0期和G1早期低表达，在G1晚期表达升高，在S和G2期表达达到高峰。Skp2的失活导致了S/G2期核内倍增和多种中心体细胞的停止(4)。Skp2的过度表达导致CDK活性的增加，并导致癌症细胞的增殖降解以及遗传不稳定性(7)。研究表明Skp2的增加和p27水平的降低，与多种进展性淋巴瘤和人癌症诸如结肠、乳腺、前列腺和肺癌有关(7)。几种最近的研究表明，Skp2受磷酸化依赖的调节，该调节通过Ser/Thr激酶增殖前的网络介导。Skp2 由CDK2在Ser64磷酸化(8)，由Akt1在Ser72(9)磷酸化，PIM1在Thr417 (10)磷酸化，促进了Skp2的稳定性，可能有助于Skp2致肿瘤性的另外的机制。

1. Pagano, M. (2004) Mol Cell 14, 414-6.
2. Reed, S.I. (2003) Nat Rev Mol Cell Biol 4, 855-64.
3. Zhang, H. et al. (1995) Cell 82, 915-25.
4. Nakayama, K. et al. (2004) Dev Cell 6, 661-72.
5. Bornstein, G. et al. (2003) J Biol Chem 278, 25752-7.
6. Tedesco, D. et al. (2002) Genes Dev 16, 2946-57.
7. Bloom, J. and Pagano, M. (2003) Semin Cancer Biol 13, 41-7.
8. Rodier, G. et al. (2008) EMBO J 27, 679-91.
9. Gao, D. et al. (2009) Nat Cell Biol 11, 397-408.
10. Cen, B. et al. (2010) J Biol Chem 285, 29128-37.

原厂资料：

Specificity / Sensitivity

Skp2 (D3G5) XP® Rabbit mAb recognizes endogenous levels of total Skp2 protein. This antibody is predicted to cross-react with Skp2α and Skp2β.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the amino terminus of human Skp2 protein.

Background

Members of the F-box family of proteins are characterized by the approximate 40 amino acid F-box motif named after cyclin F (1,2). F-box proteins constitute one of the four subunits of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex. The substrate specificity of SCF complexes is determined by the interchangeable F-box proteins, which act as adaptors by associating with phosphorylated substrate proteins and recruiting them to the SCF core. F-box proteins contain two fundamental domains: the F-box motif mediates binding to Skp1 and a leucine rich repeat (LRR) domain mediates substrate interactions.S phase kinase-associated protein 2 (Skp2) interacts with cyclin A/CDK2 and mediates proper G1 to S and G2 to M phase transitions by targeting the cyclin-dependent kinase (CDK) inhibitors p27, p21, p130, and the FoxO1 transcription factor for ubiquitination and subsequent proteolysis (3-6). Skp2 protein expression is low in G0 and early G1 phase, increases during late G1 phase, and peaks during S and G2 phases. Inactivation of Skp2 results in S/G2 phase arrested cells with endoduplication and multiple centrosomes (4). Overexpression of Skp2 results in increased CDK activity and contributes to the deregulated proliferation and genetic instabilities typical of cancer cells (7). Research studies have shown that increased Skp2/decreased p27 levels are associated with many aggressive lymphomas and human carcinomas such as colon, breast, prostate and lung cancers (7). Several recent research studies have demonstrated that Skp2 is subject to phosphorylation-dependent regulation by a network of pro-proliferative Ser/Thr kinases. It appears as though phosphorylation of Skp2 at Ser64 by CDK2 (8), Ser72 by Akt1 (9), and Thr417 by PIM1 (10) promotes stabilization of Skp2, possibly constituting an additional mechanism for Skp2 oncogenicity.

1. Pagano, M. (2004) Mol Cell 14, 414-6.
2. Reed, S.I. (2003) Nat Rev Mol Cell Biol 4, 855-64.
3. Zhang, H. et al. (1995) Cell 82, 915-25.
4. Nakayama, K. et al. (2004) Dev Cell 6, 661-72.
5. Bornstein, G. et al. (2003) J Biol Chem 278, 25752-7.
6. Tedesco, D. et al. (2002) Genes Dev 16, 2946-57.
7. Bloom, J. and Pagano, M. (2003) Semin Cancer Biol 13, 41-7.
8. Rodier, G. et al. (2008) EMBO J 27, 679-91.
9. Gao, D. et al. (2009) Nat Cell Biol 11, 397-408.
10. Cen, B. et al. (2010) J Biol Chem 285, 29128-37.

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