Menin (D45B1) XP? Rabbit mAb

• 产品编号：CST-6891S      品牌：CST       原厂货号：6891S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

Menin (D45B1) XP® Rabbit mAb兔单抗能够检测内源性Menin蛋白所有3个亚型的蛋白水平。通过合成的与人源Menin蛋白Val597位点周围相应多肽片段去免疫动物从而制备出此单克隆抗体。MEN1肿瘤抑制基因可引起multiple endocrine neoplasia type 1 (MEN1)，它是一个常染色体显性遗传肿瘤综合征，代表性的有垂体、甲状旁腺、肺和enteropancreatic内分泌组织的肿瘤(1,2)。这个肿瘤综合征的病人在MEN1基因的等位基因上的错误或截断突变可以遗传，而这些病人的肿瘤中的其它等位基因受限于杂合性的减少(1,2)。MEN1基因的蛋白产物Menin是一个含有组蛋白甲基转移酶复合物的mixed-lineage leukemia protein (MLL)的成分，该复合物有助于histone H3蛋白Lys4位点的甲基化从而有助于促进转录激活(3,4)。Menin的功能是去抑制胰岛细胞的增殖，至少部分程度上通过MLL介导的p18INK4c (p18)和p27CIP/KIP (p27) 细胞周期素依赖的激酶抑制基因的激活(5,6)。Menin的减少导致histone H3蛋白Lys4位点甲基化的减少，以及p18和p27基因表达的减少，这导致畸形生长(5,6)。与在内分泌细胞中作为肿瘤抑制因子的功能比较，在白血病细胞中通过MLL融合蛋白，Menin已经显示可以促进增殖 。Menin对于致癌的MLL融合蛋白介导的骨髓细胞的转化是至关重要的，并且对于histone H3蛋白Lys4位点甲基化和Hoxa9基因的表达是需要的(7,8)。Menin可与大范围蛋白发生相互作用，包括JunD、SMAD家族成员、雌激素受体、vitamin D受体、PEM、NFκB、FANCD2、RPA2、NMMHC II-A、GFAP、vimentin和Hsp70，这些认为在转录调节、DNA复制和修复、细胞骨架组织和蛋白质降解中有额外的功能(9,10)。

1. Chandrasekharappa, S.C. et al. (1997) Science 276, 404-7.
2. Lemmens, I. et al. (1997) Hum Mol Genet 6, 1177-83.
3. Hughes, C.M. et al. (2004) Mol Cell 13, 587-97.
4. Yokoyama, A. et al. (2004) Mol Cell Biol 24, 5639-49.
5. Karnik, S.K. et al. (2005) Proc Natl Acad Sci USA 102, 14659-64.
6. Schnepp, R.W. et al. (2006) Cancer Res 66, 5707-15.
7. Yokoyama, A. et al. (2005) Cell 123, 207-18.
8. Chen, Y.X. et al. (2006) Proc Natl Acad Sci USA 103, 1018-23.
9. Agarwal, S.K. et al. (2005) Horm Metab Res 37, 369-74.
10. Wu, X. and Hua, X. (2008) Curr Mol Med 8, 805-15.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Bovine, Pig, Horse

Specificity / Sensitivity

Menin (D45B1) XP® Rabbit mAb recognizes total endogenous levels of all 3 isoforms of Menin protein.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val597 of human Menin protein.

Background

Mutations in the MEN1 tumor suppressor gene cause multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant familial tumor syndrome typified by tumors of the pituitary, parathyroid, lung, and enteropancreatic endocrine tissues (1,2). Patients with this tumor syndrome have inherited either missense or truncation mutations in one allele of the MEN1 gene, while the other allele is subject to loss of heterozygosity in tumors from these patients (1,2). Menin, the protein product of the MEN1 gene, is a component of the mixed-lineage leukemia protein (MLL)-containing histone methyltransferase complex that facilitates methylation of histone H3 Lys4 to promote transcriptional activation (3,4). Menin functions to suppress proliferation of pancreatic islet cells, at least in part through MLL-mediated activation of the p18INK4c (p18) and p27CIP/KIP (p27) cyclin-dependent kinase inhibitor genes (5,6). Loss of Menin leads to a decrease in methylation of histone H3 Lys4 and decreased expression of the p18 and p27 genes, leading to hyperplasia (5,6). In contrast to its role as a tumor suppressor in endocrine cells, Menin has been shown to promote proliferation in leukemia cells driven by MLL-fusion proteins. Menin is essential for oncogenic MLL-fusion-protein-mediated transformation of bone marrow cells and is required for histone H3 Lys4 methylation and expression of the Hoxa9 gene (7,8). Menin interacts with a wide range of proteins, including JunD, SMAD family members, estrogen receptor, vitamin D receptor, PEM, NFκB, FANCD2, RPA2, NMMHC II-A, GFAP, vimentin, and Hsp70 suggesting additional roles in transcriptional regulation, DNA processing and repair, cytoskeleton organization, and protein degradation (9,10).

1. Chandrasekharappa, S.C. et al. (1997) Science 276, 404-7.
2. Lemmens, I. et al. (1997) Hum Mol Genet 6, 1177-83.
3. Hughes, C.M. et al. (2004) Mol Cell 13, 587-97.
4. Yokoyama, A. et al. (2004) Mol Cell Biol 24, 5639-49.
5. Karnik, S.K. et al. (2005) Proc Natl Acad Sci USA 102, 14659-64.
6. Schnepp, R.W. et al. (2006) Cancer Res 66, 5707-15.
7. Yokoyama, A. et al. (2005) Cell 123, 207-18.
8. Chen, Y.X. et al. (2006) Proc Natl Acad Sci USA 103, 1018-23.
9. Agarwal, S.K. et al. (2005) Horm Metab Res 37, 369-74.
10. Wu, X. and Hua, X. (2008) Curr Mol Med 8, 805-15.

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.