Phospho-DBC1 (Thr454) Antibody

• 产品编号：CST-4880S      品牌：CST       原厂货号：4880S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-DBC1 (Thr454) Antibody能够检测仅在Thr454位点磷酸化的内源性DBC1总蛋白水平。通过合成的与人源DBC1蛋白Thr454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。

Deleted in breast cancer gene 1 protein (DBC1)最初通过它定位到染色体8p21区域被鉴定，它在乳腺癌中纯合子的缺失(1)。在存活的细胞中，DBC1蛋白是一个具有多种功能的分子量大的细胞核蛋白。它以非配体依赖性方式直接结合到雌激素受体 (strogen receptor α，ERα)激素结合区域，并且可能是非配体ERα 表达和存在人源乳腺癌细胞系中的一个关键因素(2)。DBC1蛋白可能通过结合到和抑制SirT1蛋白的去乙酰酶活性从而促进p53介导的凋亡，这导致p53乙酰化水平和活性的增加(3)。DBC1蛋白可能是一个重要异染色质形成的调节因子，因为它结合SUV39H1以及抑制它的组蛋白甲基转移酶活性(4)。在Tumor Necrosis Factor-α (TNF-α)介导的细胞死亡信号期间，Caspase依赖的进程可以激活DBC1的促凋亡活性(5)。在TNF-α刺激下，DBC1蛋白的这个过程发生在凋亡的初期，并且导致DBC1蛋白重新定位到细胞质。DBC1蛋白的加工的细胞质形式的过量表达导致线粒体的群集和基质浓缩，并且使得细胞对于TNF-α介导凋亡敏感。

在DNA损伤下，DBC1蛋白的454位点threonine残基以一个ATM/ATR依赖的方式被磷酸化(6,7)。Cell Signaling Technology (CST)使用PhosphoScan®, CST's LC-MS/MS平台发现磷酸化位点，因此Phospho-DBC1 (Thr454) Antibody直接作用于该位点。使用一个ATM/ATR底物抗体去检测Thr454位点的磷酸化，并且通过UV照射诱导其磷酸化。请访问PhosphoSitePlus®, CST's modification网站：www.phosphosite.org for more information。

1. Hamaguchi, M. et al. (2002) Proc Natl Acad Sci USA 99, 13647-52.
2. Trauernicht, A.M. et al. (2007) Mol Endocrinol 21, 1526-36.
3. Zhao, W. et al. (2008) Nature 451, 587-90.
4. Li, Z. et al. (2009) J Biol Chem 284, 10361-6.
5. Sundararajan, R. et al. (2005) Oncogene 24, 4908-20.
6. Stokes, M.P. et al. (2007) Proc Natl Acad Sci USA 104, 19855-60.
7. Beausoleil, S.A. et al. (2004) Proc Natl Acad Sci USA 101, 12130-5.

原厂资料：

Specificity / Sensitivity

Phospho-DBC1 (Thr454) Antibody detects endogenous levels of DBC1 only when phosphorylated on Thr454.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to Thr454 of the human DBC1 protein. Antibodies are purified by protein A and peptide affinity chromatography.

Background

Deleted in breast cancer gene 1 protein (DBC1) was originally identified by its localization to a region of chromosome 8p21 that is homozygously deleted in breast cancer (1). DBC1 is a large, nuclear protein with multiple functions in cell survival. It binds directly to the estrogen receptor α (ERα) hormone-binding domain in a ligand-independent manner and may be a key determinant of ligand-independent ERα expression and survival in human breast cancer cells (2). DBC1 can promote p53-mediated apoptosis by binding to and inhibiting the deacetylase activity of SirT1, resulting in increased p53 acetylation levels and activity (3). DBC1 may be an important regulator of heterochromatin formation as it binds SUV39H1 and inhibits its histone methyltransferase activity (4). Caspase-dependent processing activates the pro-apoptotic activity of DBC1 during Tumor Necrosis Factor-α (TNF-α)-mediated cell death signaling (5). This processing of DBC1 in response to TNF-α is an early event in the onset of apoptosis and results in relocalization of DBC1 to the cytoplasm. Overexpression of the processed, cytoplasmic form of DBC1 results in mitochondrial clustering and matrix condensation and sensitizes cells to TNF-α-mediated apoptosis.

The threonine residue at 454 of DBC1 is phosphorylated in an ATM/ATR-dependent manner in response to DNA damage (6,7). Phospho-DBC1 (Thr454) Antibody is directed at a site that was identified at Cell Signaling Technology (CST) using PhosphoScan®, CST's LC-MS/MS platform for modification site discovery. Phosphorylation at Thr454 was discovered using an ATM/ATR substrate antibody and was shown to be induced by UV treatment. Please visit PhosphoSitePlus®, CST's modification site knowledgebase, at www.phosphosite.org for more information.

1. Hamaguchi, M. et al. (2002) Proc Natl Acad Sci USA 99, 13647-52.
2. Trauernicht, A.M. et al. (2007) Mol Endocrinol 21, 1526-36.
3. Zhao, W. et al. (2008) Nature 451, 587-90.
4. Li, Z. et al. (2009) J Biol Chem 284, 10361-6.
5. Sundararajan, R. et al. (2005) Oncogene 24, 4908-20.
6. Stokes, M.P. et al. (2007) Proc Natl Acad Sci USA 104, 19855-60.
7. Beausoleil, S.A. et al. (2004) Proc Natl Acad Sci USA 101, 12130-5.

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.