Huntingtin (D7F7) XP? Rabbit mAb

• 产品编号：CST-5656S      品牌：CST       原厂货号：5656S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Huntingtin (D7F7) XP® Rabbit mAb 识别内源性的总huntingtin蛋白。该单克隆抗体由合成的人类huntingtin蛋白Pro1220位点附近肽段免疫动物而制成。亨廷顿舞蹈症（HD）是一种致命的神经退行性疾病，以精神、认知和运动功能障碍为特征。HD的神经病理学涉及特定的神经元亚群：纹状体和大脑皮层GABA能神经元选择性变性（1,2）。对HD的遗传分析进展卓越，已经从最初的染色体定位进步到现在的基因识别。Huntingtin是一个大（340-350 KD）的胞浆蛋白，可能参与细胞的如转录，原肠期发育，神经生长，神经传导，轴突运输，神经定位，以及细胞凋亡等功能，（2,3）。正常人的HD基因包含6-34个CAG三联核苷酸重复序列，超过这个范围的重复将导致症状出现。发病年龄与huntingtin基因CAG重复序列有很强的负相关（1,2）。huntingtin蛋白的转录后修饰包括磷酸化、泛素化、SUMO化、棕榈酰化和剪切（2）。Akt可以磷酸化Ser421位点，对抗过多的多聚谷氨酸序列带来的毒性。大脑中不同的Akt的表达与不同区域亨廷顿蛋白的磷酸化水平有相关；与病变脑区退行性变的区域负相关（2）。疾病进程的关键步骤就是这个将huntingtin蛋白切割为包含谷氨酸重复序列的氨基末端片段，然后在翻译到细胞核中去。Caspase介导的huntingtin Asp513切断与多聚谷氨酸积累和毒性有关。CDK5磷酸化Ser434可以对抗这种剪切（2,3）。

1. Gusella, J.F. and Macdonald, M.E. (2006) Trends Biochem. Sci. 31, 533-540.
2. Borrell-Pagès, M. et al. (2006) Cell Mol. Life Sci. 63, 2642-2660.
3. Luo, S. et al. (2005) J. Cell Biol. 169, 647-656.

原厂资料：

Specificity / Sensitivity

Huntingtin (D7F7) XP® Rabbit mAb detects endogenous levels of total huntingtin protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro1220 of human huntingtin protein.

Background

Huntingtin Disease (HD) is a fatal neurodegenerative disorder characterized by psychiatric, cognitive, and motor dysfunction. Neuropathology of HD involves specific neuronal subpopulations: GABA-ergic neurons of the striatum and neurons within the cerebral cortex selectively degenerate (1,2). The genetic analysis of HD has been the flagship study of inherited neurological diseases from initial chromosomal localization to identification of the gene. 
 Huntingtin is a large (340-350 kD) cytosolic protein that may be involved in a number of cellular functions such as transcription, gastrulation, neurogenesis, neurotransmission, axonal transport, neural positioning, and apoptosis (2,3). The HD gene from unaffected individuals contains between 6 and 34 CAG trinucleotide repeats, with expansion beyond this range causing the onset of disease symptoms. A strong inverse correlation exists between the age of onset in patients and the number of huntingtin gene CAG repeats encoding a stretch of polyglutamine peptides (1,2). The huntingtin protein undergoes numerous post-translational modifications including phosphorylation, ubiquitination, sumoylation, palmitoylation, and cleavage (2). Phosphorylation of Ser421 by Akt can partially counteract the toxicity that results from the expanded polyglutamine tract. Varying Akt expression in the brain correlates with regional differences in huntingtin protein phosphorylation; this pattern inversely correlates with the regions that are most affected by degeneration in diseased brain (2). A key step in the disease is the proteolytic cleavage of huntingtin protein into amino-terminal fragments that contain expanded glutamine repeats and translocate into the nucleus. Caspase mediated cleavage of huntingtin at Asp513 is associated with increased polyglutamine aggregate formation and toxicity. Phosphorylation of Ser434 by CDK5 protects against cleavage (2,3).

1. Gusella, J.F. and Macdonald, M.E. (2006) Trends Biochem. Sci. 31, 533-540.
2. Borrell-Pagès, M. et al. (2006) Cell Mol. Life Sci. 63, 2642-2660.
3. Luo, S. et al. (2005) J. Cell Biol. 169, 647-656.

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.