NCoR1 Antibody

• 产品编号：CST-5948S      品牌：CST       原厂货号：5948S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

NCoR1 Antibody检测内源性NCoR1总蛋白水平。该抗体不与SMRT/NCoR2发生交叉反应。通过合成的人源NCoR1蛋白Pro1387位点周围相应多肽片段去免疫动物从而制备此多克隆抗体。通过蛋白A和多肽亲和层析纯化获得。最具特征的细胞核受体辅助抑制因子是SMRT(silencing mediator for retinoic acid and thyroid hormone receptors)，并且它的紧密的间接同源物NCoR1 (nuclear receptor corepressor) (1,2)。NCoR1的功能是转录沉默多种非配体化的、DNA结合的非甾体类细胞核受体，这通过作为一个大分子支架去桥接多种染色质重塑因子的受体，这些重塑分子能够抑制细胞核受体介导的基因转录，部分程度上通过靶基因启动子周围的中心组蛋白去乙酰化。的确，NCoR1蛋白的N端部分拥有多种明显的转录抑制区域(RDs)，这就解释了辅助抑制因子复合物例如HDACs、mSin3、GPS2和TBL1/TBLR1额外成分的招募。在RDs区域之间存在一对潜在的抑制结构成为SANT motifs (SWI3、ADA2、N-CoR、TFIIIB)，这能招募HDAC3和组蛋白到抑制因子复合物上从而提高了HDAC3活性(3)。NCoR1蛋白的C端部分包含多种细胞核受体结合区域(NDs)，它们的每一个都包含一个保守的CoRNR box (or L/I-X-X-I/V-I) motif，这就允许结合到多种非配体的细胞核激素受体例如甲状腺激素(THR)和视黄酸(RAR)受体(4,5)。最近在小鼠的基因学研究中不但证实了涉及NCoR1蛋白的生物化学研究的财富，也提供了重要意义的方向是关于NCoR1在哺乳动物的发育和生理的功能。虽然研究发现Ncor1的缺失不能影响早期胚胎发育，很可能是由于 Smrt的补偿作用，但是胚胎的致死基本上是发生在怀孕的中期，很大程度上由于erythropoesis和thymopoesis缺陷(6)。另外的研究证明NCoR1蛋白的NDs对于在一个作为肝的THR和Liver X Receptor (LXR)的转录抑制因子的生理过程起到至关重要的作用(7)。

1. Chen, J.D. and Evans, R.M. (1995) Nature 377, 454-7.
2. Hörlein, A.J. et al. (1995) Nature 377, 397-404.
3. Jones, P.L. and Shi, Y.B. (2003) Curr Top Microbiol Immunol 274, 237-68.
4. Downes, M. et al. (1996) Nucleic Acids Res 24, 4379-86.
5. Wong, C.W. and Privalsky, M.L. (1998) Mol Cell Biol 18, 5724-33.
6. Jepsen, K. et al. (2000) Cell 102, 753-63.
7. Astapova, I. et al. (2008) Proc Natl Acad Sci U S A 105, 19544-9.

原厂资料：

Specificity / Sensitivity

NCoR1 Antibody recognizes endogenous levels of total NCoR1 protein. This antibody does not cross-react with SMRT/NCoR2.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Pro1387 of human NCoR1 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

The most well characterized nuclear receptor corepressors are SMRT (silencing mediator for retinoic acid and thyroid hormone receptors) and its close paralog NCoR1 (nuclear receptor corepressor) (1,2). NCoR1 functions to transcriptionally silence various unliganded, DNA bound non-steroidal nuclear receptors by serving as a large molecular scaffold that bridges the receptors with multiple chromatin remodeling factors that repress nuclear receptor-mediated gene transcription, in part, through deacetylation of core histones surrounding target promoters. Indeed, the N-terminal portion of NCoR1 possesses multiple distinct transcriptional repression domains (RDs) reponsible for the recruitment of additional components of the corepressor complex such as HDACs, mSin3, GPS2, and TBL1/TBLR1. In between the RDs lies a pair of potent repressor motifs known as SANT motifs (SWI3, ADA2, N-CoR, and TFIIIB), which recruit HDAC3 and histones to the repressor complex in order to enhance HDAC3 activity (3). The C-terminal portion of NCoR1 contains multiple nuclear receptor interaction domains (NDs), each of which contains a conserved CoRNR box (or L/I-X-X-I/V-I) motif that allow for binding to various unliganded nuclear hormone receptors such as thyroid hormone (THR) and retinoic acid (RAR) receptors (4,5). 
 
 Recent genetic studies in mice have not only corroborated the wealth of biochemical studies involving NCoR1 but have also provided significant insight regarding the function of NCoR1 in mammalian development and physiology. Although it has been observed that loss of Ncor1 does not affect early embyonic development, likely due to compensation by Smrt, embryonic lethality ultimately results during mid-gestation, largely due to defects in erythropoesis and thymopoesis (6). Another study demonstrated that the NDs of NCoR1 are critical for its ability to function in a physiological setting as a transcriptional repressor of hepatic THR and Liver X Receptor (LXR) (7).

1. Chen, J.D. and Evans, R.M. (1995) Nature 377, 454-7.
2. Hörlein, A.J. et al. (1995) Nature 377, 397-404.
3. Jones, P.L. and Shi, Y.B. (2003) Curr Top Microbiol Immunol 274, 237-68.
4. Downes, M. et al. (1996) Nucleic Acids Res 24, 4379-86.
5. Wong, C.W. and Privalsky, M.L. (1998) Mol Cell Biol 18, 5724-33.
6. Jepsen, K. et al. (2000) Cell 102, 753-63.
7. Astapova, I. et al. (2008) Proc Natl Acad Sci U S A 105, 19544-9.

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