HDAC3 (7G6C5) Mouse mAb

• 产品编号：CST-3949P      品牌：Cell Signaling Technology       原厂货号：3949P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

HDAC3 (7G6C5) Mouse mAb鼠单抗能够检测内源性HDAC3总蛋白水平。该抗体不能源其它HDAC蛋白发生交叉反应。通过重组人源HDAC3蛋白去免疫动物从而制备出此单克隆抗体。

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)。

HDAC3是一个细胞核和细胞质蛋白，它能使histone (H2A、H3、H4)和非组蛋白底物(RelA、SRY、p53、MEF2、PCAF和p300/CBP)发生去乙酰化(8)。HDAC3去乙酰化活性通过N-CoR和SMRT共抑制蛋白的相互作用而被刺激。同时，这三个蛋白形成一个功能性复合物，该复合物能抑制与细胞核激素受体和其它转录因子转录，包括Rev-Erb、COUP-TF、DAX1、MAD和Pit-1 (8,9)。由casein kinase 2 (CK2)使HDAC3在Ser424位点的磷酸化也恩呢该增加HDAC3去乙酰化活性(9)。随后，通过蛋白磷酸酶4(protein phosphatase 4 ,PP4) 的去磷酸化可降低HDAC3活性(9)。

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. Karagianni, P. and Wong, J. (2007) Oncogene 26, 5439-5449.
9. Zhang, X. et al. (2005) Genes Dev. 19, 827-839.

原厂资料：

Specificity / Sensitivity

HDAC3 (7G6C5) Mouse mAb detects endogenous levels of total HDAC3 protein. The antibody does not cross-react with other HDAC proteins.

Source / Purification

Monoclonal antibody is produced by immunizing animals with recombinant human HDAC3 protein.

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).

HDAC3 is a nuclear and cytoplasmic protein that deacetylates both histone (H2A, H3, H4) and non-histone substrates (RelA, SRY, p53, MEF2, PCAF and p300/CBP) (8). HDAC3 deacetylase activity is stimulated by interactions with the N-CoR and SMRT co-repressor proteins. Together, these three proteins form a functional complex that represses transcription associated with nuclear hormone receptors and other transcription factors, including Rev-Erb, COUP-TF, DAX1, MAD and Pit-1 (8,9). Phosphorylation of HDAC3 on Ser424 by casein kinase 2 (CK2) also increases HDAC3 deacetylase activity (9). Subsequently, de-phosphorylation by protein phosphatase 4 (PP4) decreases HDAC3 activity (9).

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. Karagianni, P. and Wong, J. (2007) Oncogene 26, 5439-5449.
9. Zhang, X. et al. (2005) Genes Dev. 19, 827-839.

注意事项：

Storage: Supplied in 10 mM 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