Phospho-HDAC4 (Ser632)/HDAC5 (Ser661)/HDAC7 (Ser486) Antibody

• 产品编号：CST-3424S      品牌：CST       原厂货号：3424S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-HDAC4 (Ser632)/HDAC5 (Ser498)/HDAC7 (Ser486) Antibody能够分别检测Ser632、Ser498和Ser486位点磷酸化的内源性HDAC4、HDAC5和HDAC7的蛋白水平。该抗体也与未知蛋白80 kDa大小发生交叉反应。通过合成的与人源HDAC7蛋白Ser486位点周围相应的磷酸化片段去免疫动物从而制备出此多克隆抗体。通过蛋白A和多肽亲和层析纯化获得。

组蛋白尾部的乙酰化可引起染色质成为松散的构象，这允许转录因子更易接近DNA。组蛋白去乙酰化转移酶(histone acetyltransferases,HATs)的鉴定和它们的多种蛋白复合物在它们怎样酶促调节转录中已经有了重要的见解(1,2)。HAT复合物可与特异性靶基因上序列特异的激活蛋白发生相互作用。除了组蛋白之外，HATs能够使非组蛋白乙酰化，这就认为这些酶的多种功能(3)。与此相反，组蛋白去乙酰化可促进一个致密的染色质构象，并且典型地导致基因活性的抑制(4)。哺乳动物组蛋白去乙酰化酶能按照它们的类似与多种酵母去乙酰化酶划分成三类(5)。Class I蛋白 (HDACs 1、2、3和8)是与酵母Hda1样蛋白相关，并且class III蛋白是与酵母Sir2相关。目前HDAC活性的抑制剂已经被认为潜在的治疗癌症的药物(6,7)。

Histone deacetylases (HDACs)与越来越多的转录因子相互作用，包括myocyte enhancer factor 2 (MEF2)，目的是负性调节基因表达。HDACs部分程度上通过在细胞核和细胞质中穿梭来被调节，在细胞质内通过从它们的靶基因上移去HDACs从而有助于基因激活(8,9)。14-3-3蛋白有助于细胞质的输出，这主要是结合到HDAC蛋白上的特异性磷酸化丝氨酸残基(8,9)。在HDAC蛋白之间这些磷酸化丝氨酸14-3-3结合模式是高度保守的，在特定的细胞刺激下这允许它们的共同调节。例如，在多种细胞刺激下高度保守的HDAC4 Ser246位点、HDAC5 Ser259位点和HDAC7 Ser155位点残基通过CAMK和PKD激酶被磷酸化，包括在内皮细胞、B细胞和T细胞激活中VEGF诱导的血管生成，以及成肌细胞分化成肌纤维(10-14)。

1. Marmorstein, R. (2001) Cell Mol Life Sci 58, 693-703.
2. Gregory, P.D. et al. (2001) Exp Cell Res 265, 195-202.
3. Liu, Y. et al. (2000) Mol Cell Biol 20, 5540-53.
4. Cress, W.D. and Seto, E. (2000) J Cell Physiol 184, 1-16.
5. Gray, S.G. and Ekström, T.J. (2001) Exp Cell Res 262, 75-83.
6. Thiagalingam, S. et al. (2003) Ann. N.Y. Acad. Sci. 983, 84-100.
7. Vigushin, D.M. and Coombes, R.C. (2004) Curr. Cancer Drug Targets 4, 205-218.
8. Grozinger, C.M. and Schreiber, S.L. (2000) Proc Natl Acad Sci USA 97, 7835-40.
9. Wang, A.H. et al. (2000) Mol Cell Biol 20, 6904-12.
10. Ha, C.H. et al. (2008) J Biol Chem 283, 14590-9.
11. Wang, S. et al. (2008) Proc Natl Acad Sci U S A 105, 7738-43.
12. Matthews, S.A. et al. (2006) Mol Cell Biol 26, 1569-77.
13. Parra, M. et al. (2005) J Biol Chem 280, 13762-70.
14. McKinsey, T.A. et al. (2000) Nature 408, 106-11.

原厂资料：

Specificity / Sensitivity

Phospho-HDAC4 (Ser632)/HDAC5 (Ser498)/HDAC7 (Ser486) Antibody detects endogenous levels of HDAC4, HDAC5 and HDAC7 proteins only when phosphorylated on Ser632, Ser498 and Ser486, respectively. The antibody also crossreacts with an unidentified protein at 80 kDa.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to human HDAC7 protein phosphorylated on Ser486. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Acetylation of the histone tail causes chromatin to adopt an "open" conformation, allowing increased accessibility of transcription factors to DNA. The identification of histone acetyltransferases (HATs) and their large multiprotein complexes has yielded important insights into how these enzymes regulate transcription (1,2). HAT complexes interact with sequence-specific activator proteins to target specific genes. In addition to histones, HATs can acetylate nonhistone proteins, suggesting multiple roles for these enzymes (3). In contrast, histone deacetylation promotes a "closed" chromatin conformation and typically leads to repression of gene activity (4). Mammalian histone deacetylases can be divided into three classes on the basis of their similarity to various yeast deacetylases (5). Class I proteins (HDACs 1, 2, 3, and 8) are related to the yeast Rpd3-like proteins, those in class II (HDACs 4, 5, 6, 7, 9, and 10) are related to yeast Hda1-like proteins, and class III proteins are related to the yeast protein Sir2. Inhibitors of HDAC activity are now being explored as potential therapeutic cancer agents (6,7).

Histone deacetylases (HDACs) interact with an increasing number of transcription factors, including myocyte enhancer factor 2 (MEF2), to negatively regulate gene expression. HDACs are regulated in part by shuttling between the nucleus and cytoplasm, where export to the cytoplasm facilitates gene activation by removing HDACs from their target genes (8,9). The cytoplasmic export is facilitated by 14-3-3 proteins, which bind to specific phospho-serine residues on the HDAC proteins (8,9). These phospho-serine 14-3-3 binding modules are highly conserved between HDAC proteins, allowing for their collective regulation in response to specific cell stimuli. For example, the highly conserved HDAC 4 Ser632, HDAC 5 Ser498 and HDAC 7 Ser486 residues are all phosphorylated by CAMK and PKD kinases in response to multiple cell stimuli, including VEGF-induced angiogenesis in endothelial cells, B cell and T cell activation, and differentiation of myoblasts into muscle fiber (10-14).

1. Marmorstein, R. (2001) Cell Mol Life Sci 58, 693-703.
2. Gregory, P.D. et al. (2001) Exp Cell Res 265, 195-202.
3. Liu, Y. et al. (2000) Mol Cell Biol 20, 5540-53.
4. Cress, W.D. and Seto, E. (2000) J Cell Physiol 184, 1-16.
5. Gray, S.G. and Ekström, T.J. (2001) Exp Cell Res 262, 75-83.
6. Thiagalingam, S. et al. (2003) Ann. N.Y. Acad. Sci. 983, 84-100.
7. Vigushin, D.M. and Coombes, R.C. (2004) Curr. Cancer Drug Targets 4, 205-218.
8. Grozinger, C.M. and Schreiber, S.L. (2000) Proc Natl Acad Sci USA 97, 7835-40.
9. Wang, A.H. et al. (2000) Mol Cell Biol 20, 6904-12.
10. Ha, C.H. et al. (2008) J Biol Chem 283, 14590-9.
11. Wang, S. et al. (2008) Proc Natl Acad Sci U S A 105, 7738-43.
12. Matthews, S.A. et al. (2006) Mol Cell Biol 26, 1569-77.
13. Parra, M. et al. (2005) J Biol Chem 280, 13762-70.
14. McKinsey, T.A. et al. (2000) Nature 408, 106-11.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.