Cell Signaling Technology

Product Pathways - Chromatin Regulation / Epigenetics

JMJD2B (D7E6) Rabbit mAb #8639

No. Size Price
8639S 100 µl ( 10 western blots ) ¥3,100.00 现货查询 购买询价
8639 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Monkey, Endogenous 150 Rabbit IgG
IP 1:50
IF-IC 1:800

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting, IP=Immunoprecipitation, IF-IC=Immunofluorescence (Immunocytochemistry),

Specificity / Sensitivity

JMJD2B (D7E6) Rabbit mAb recognizes endogenous levels of total JMJD2B protein. This antibody does not cross-react with other Jumonji C proteins, including JMJD2A, JMJD2C, and JMJD2D.

JMJD2B (D7E6) Rabbit mAb兔单抗能够检测内源性JMJD2B总蛋白水平。该抗体不与其它Jumonji C 蛋白发生交叉反应,包括JMJD2A、JMJD2C或JMJD2D蛋白。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human JMJD2B protein.

通过合成的与人源JMJD2B蛋白羧基端相应的多肽片段去免疫动物从而制备出此单克隆抗体。

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using JMJD2B (D7E6) Rabbit mAb.

使用JMJD2B (D7E6) Rabbit mAb兔单抗,免疫印迹(Western blot)分析不同细胞中JMJD2B的蛋白水平。

IF-IC

IF-IC

Confocal immunofluorescent analysis of LNCaP cells using JMJD2B (D7E6) Rabbit mAb (green). Actin filaments were labeled with DY-554 phalloidin (red).

使用JMJD2B (D7E6) Rabbit mAb兔单抗 (绿色),共聚焦免疫荧光分析LNCaP细胞。DY-554 phalloidin标记微丝蛋白(红色)。

Background

The methylation state of lysine residues in histone proteins is a major determinant of the formation of active and inactive regions of the genome and is crucial for proper programming of the genome during development (1,2). Jumonji C (JmjC) domain-containing proteins represent the largest class of potential histone demethylase proteins (3). The JmjC domain can catalyze the demethylation of mono-, di-, and tri-methyl lysine residues via an oxidative reaction that requires iron and α-ketoglutarate (3). Based on homology, both humans and mice contain at least 30 such proteins, which can be divided into 7 separate families (3). The jumonji domain-containing protein 2 (JMJD2) family, also known as the JmjC domain-containing histone demethylation protein 3 (JHDM3) family, contains four members: JMJD2A/JHDM3A, JMJD2B/JHDM3B, JMJD2C/JHDM3C, and JMJD2D/JHDM3D. In addition to the JmjC domain, these proteins also contain JmjN, PHD, and tudor domains, the latter of which has been shown to bind to methylated histone H3 at Lys4 and Lys9, and methylated histone H4 at Lys20 (4,5). JMJD2 proteins have been shown to demethylate di- and tri-methyl histone H3 at Lys9 and Lys36 and function as both activators and repressors of transcription (6-11). JMJD2A, JMJD2C, and JMJD2D function as coactivators of the androgen receptor in prostate tumor cells (7). In contrast, JMJD2A also associates with Rb and NCoR corepressor complexes and is necessary for transcriptional repression of target genes (8,9). JMJD2B antagonizes histone H3 Lys9 tri-methylation at pericentric heterochromatin (10). JMJD2C, also known as GASC1, is amplified in squamous cell carcinomas and metastatic lung carcinoma and inhibition of JMJD2C expression decreases cell proliferation (11,12). JMJD2C has also been identified as a downstream target of Oct-4 and is critical for the regulation of self-renewal in embryonic stem cells (13).

Recent studies have demonstrated that JMJD2B is physically associated with and an integral component of the mixed-lineage leukemia (MLL) 2 H3K4 methyltransferase complex. JMJD2B also interacts with estrogen receptor α (ERα) and members of a chromatin remodeling complex, SWI/SNF-B. It is likely that JMJD2B removes repressive histone marks at ERα binding sites, which may also generate docking sites for enzymes and transcription factors that remodel chromatin in order to facilitate ERα-mediated transcription. Of note, JMJD2B is expressed in a high percentage of human breast tumors and its expression positively correlates with ERα expression. Researchers have shown that JMJD2B is a transcriptional target of ERα and may participate in a feed-forward regulatory loop involved in driving estrogen responsive breast tumor formation (14,15).

组蛋白赖氨酸的甲基化水平对于基因组的活化和非活化区域的形成是主要决定因素,并且在发育期间对于基因组的正确进程起着关键作用(1,2)。包含蛋白质的Jumonji C (JmjC)区域代表最大的潜在组蛋白去乙酰化酶蛋白(3)。JmjC区域通过氧化反应能催化单、双和三甲基化的赖氨酸残基的去乙甲基化,这种氧化反应需要铁离子和α-酮戊二酸(3)。基于同源性,人源和小鼠都包含至少30种这样蛋白质,这能够被分为7个不同的家族(3)。JMJD2 (Jumonji domain-containing protein 2)家族也称为JHDM3 (JmjC domain-containing histone demethylation protein 3)家族,包含四个成员:JMJD2A/JHDM3A、JMJD2B/JHDM3B、JMJD2C/JHDM3C和JMJD2D/JHDM3D。除了JmJC结构域之外,这些蛋白质也包含JmJN、PHD和Tudor结构域,而后者基因证明能结合到甲基化的histone H3蛋白Lys4和Lys9 位点,以及甲基化的histone H4蛋白Lys20位点上(4,5)。研究证明JMJD2蛋白可以使双核三甲基化的histone H3蛋白Lys9和Lys36位点上去甲基化,并且具有转录的激活和抑制因子的功能(6-11)。JMJD2A、JMJD2C 和JMJD2D作为在前列腺肿瘤细胞中雄激素受体的共激活因子(7)。与此相反,JMJD2A也与Rb和N-CoR共抑制因子复合物有关联,并且对于靶基因的转录抑制是必须的(8,9)。在着丝点周围异染色质上JMJD2B蛋白抑制histone H3蛋白Lys9位点三甲基化(10)。JMJD2C也称为GASC1,它在鳞状细胞癌和转移性肺癌中扩增,并且JMJD2C蛋白表达的抑制减少了细胞扩增(11,12)。JMJD2C蛋白也被鉴定作为Oct-4的下游靶蛋白,并且在胚胎干细胞中对于自我更新的调节起到重要作用(13)。

最近研究证明 JMJD2B在生理上与mixed-lineage leukemia (MLL) 2 H3K4甲基化转移酶复合物有关,并且是该复合物的一个组成部分。JMJD2B也与estrogen receptor α (ERα)和染色质重塑复合物的成员SWI/SNF-B相互作用。很可能JMJD2B可移除在ERα结合位点的抑制性组蛋白标志,该结合位点也可能产生相关酶和转录因子的停留位点,而这些转录因子是为了有助于ERα介导的转录而改造染色质的。众所周知,JMJD2B蛋白表达在人源乳腺癌百分率很高,并且它的表达与ERα表达正相关。研究者显示JMJD2B蛋白是ERα的一个转录靶点,并且可能参与正反馈调节环,该反馈涉及促进雌激素反应下肿瘤形成(14,15)。

  1. Kubicek, S. et al. (2006) Ernst Schering Res Found Workshop , 1-27.
  2. Lin, W. and Dent, S.Y. (2006) Curr Opin Genet Dev 16, 137-42.
  3. Klose, R.J. et al. (2006) Nat Rev Genet 7, 715-27.
  4. Chen, Z. et al. (2007) Proc Natl Acad Sci USA 104, 10818-23.
  5. Lee, J. et al. (2008) Nat Struct Mol Biol 15, 109-11.
  6. Whetstine, J.R. et al. (2006) Cell 125, 467-81.
  7. Shin, S. and Janknecht, R. (2007) Biochem Biophys Res Commun 359, 742-6.
  8. Gray, S.G. et al. (2005) J Biol Chem 280, 28507-18.
  9. Zhang, D. et al. (2005) Mol Cell Biol 25, 6404-14.
  10. Fodor, B.D. et al. (2006) Genes Dev 20, 1557-62.
  11. Cloos, P.A. et al. (2006) Nature 442, 307-11.
  12. Italiano, A. et al. (2006) Cancer Genet Cytogenet 167, 122-30.
  13. Loh, Y.H. et al. (2007) Genes Dev 21, 2545-57.
  14. Shi, L. et al. (2011) Proc Natl Acad Sci USA 108, 7541-6.
  15. Kawazu, M. et al. (2011) PLoS One 6, e17830.

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Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

Cell Signaling Technology® is a trademark of Cell Signaling Technology, Inc.

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