Phospho-Cyclin D1 (Thr286) (D29B3) XP? Rabbit mAb

• 产品编号：CST-3300S      品牌：CST       原厂货号：3300S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

 Phospho-Cyclin D1 (Thr286) (D29B3) XP® Rabbit mAb能够检测内源性苏氨酸（286位点）磷酸化的cyclin D1蛋白，且不与cyclin D家族其他成员发生交叉反应。该单克隆抗体是由合成的针对cyclin D1蛋白的苏氨酸（286位点）磷酸化肽段免疫动物生产的。细胞周期蛋白依赖性蛋白激酶CDK4和CDK6的活性受三个因素的调控：T-环路磷酸化，周期蛋白伴侣(D-型周期蛋白)的丰度，与CDK抑制剂Cip/Kip 或 INK蛋白家族的关系(1)。失活的三元复合物cyclin D/CDK4 和p27 Kip1需要胞外有丝分裂刺激因子参与p27伴侣的释放和降解，伴随周期蛋白D的水平升高，通过限制点和pRb依赖性的S期进入影响细胞周期的进程(2)。活跃的cyclin D/CDK4复合体靶向视网膜母细胞瘤蛋白以利于磷酸化，促进可以激活G1/S期基因表达的转录因子E2F的释放(3)。生长因子退出后，通过下调蛋白表达和磷酸化依赖性蛋白降解，周期蛋白D的水平下降(4)。Cyclin D1的异常表达与许多形式的肿瘤相关，包括B细胞淋巴瘤。cyclin D1基因的转位或扩增可以直接促进肿瘤发生。Cyclin D1在乳腺组织成熟的过程中也起到了决定性的作用。通过GSK3或者Ras/Raf/MEK/MAPK途径使Cyclin D1 苏氨酸286位点磷酸化可以加强其泛素化和蛋白酶体降解。

1. Hirai, H. et al. (1995) Mol. Cell. Biol. 15, 2672-2681.
2. Sherr, C.J. (1996) Science 274, 1672-1677.
3. Lukas, J. et al. (1996) Mol. Cell. Biol. 16, 6917-6925.
4. Diehl, J.A. et al. (1997) Genes Dev. 11, 957-972.
5. Sicinski, P. et al. (1995) Cell 82, 621-630.
6. Shao, J. et al. (2000) J Biol Chem 275, 22916-24.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-Cyclin D1 (Thr286) (D29B3) XP® Rabbit mAb detects endogenous levels of cyclin D1 only when phosphorylated at Thr286. The antibody does not cross-react with other cyclin D family members.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Thr286 of cyclin D1.

Background

Activity of the cyclin-dependent kinases CDK4 and CDK6 is regulated by T-loop phosphorylation, by the abundance of their cyclin partners (the D-type cyclins), and by association with CDK inhibitors of the Cip/Kip or INK family of proteins (1). The inactive ternary complex of cyclin D/CDK4 and p27 Kip1 requires extracellular mitogenic stimuli for the release and degradation of p27 concomitant with a rise in cyclin D levels to effect progression through the restriction point and pRb-dependent entry into S-phase (2). The active complex of cyclin D/CDK4 targets the retinoblastoma protein for phosphorylation, allowing the release of E2F transcription factors that activate G1/S-phase gene expression (3). Levels of cyclin D protein drop upon withdrawal of growth factors through downregulation of its protein expression and through phosphorylation-dependent degradation (4).

Aberrant expression of cyclin D1 is associated with many forms of cancer, including B cell lymphomas. Gene translocation or amplification of the cyclin D1 gene can directly contribute to oncogenesis (2). Cyclin D1 also plays a critical role in mammary tissue maturation (5). Phosphorylation of cyclin D1 at Thr286 by glycogen synthase kinase 3β (4) or through the Ras/Raf/MEK/MAPK pathway (6) enhances its ubiquitination and proteasomal degradation.

1. Hirai, H. et al. (1995) Mol. Cell. Biol. 15, 2672-2681.
2. Sherr, C.J. (1996) Science 274, 1672-1677.
3. Lukas, J. et al. (1996) Mol. Cell. Biol. 16, 6917-6925.
4. Diehl, J.A. et al. (1997) Genes Dev. 11, 957-972.
5. Sicinski, P. et al. (1995) Cell 82, 621-630.
6. Shao, J. et al. (2000) J Biol Chem 275, 22916-24.

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.