Cell Signaling Technology

Product Pathways - Chromatin Regulation / Epigenetics

UHRF1 (D6G8E) Rabbit mAb #12387

No. Size Price
12387S 100 µl ( 10 western blots ) ¥3,100.00 现货查询 购买询价
12387 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Mouse,Rat, Endogenous 95 Rabbit IgG
IP 1:50

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting, IP=Immunoprecipitation,

Specificity / Sensitivity

UHRF1 (D6G8E) Rabbit mAb recognizes endogenous levels of total UHRF1 protein. This antibody does not cross-react with UHRF2 protein. This antibody may recognize a non-specific 32 kDa protein in some cell lysates.

UHRF1 (D6G8E) Rabbit mAb 兔单抗能够检测内源性的UHRF1总蛋白水平。该抗体不会与 UHRF2蛋白发生交叉反应。可能还能识别一些细胞裂解物中32kDa的非特异性蛋白。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues surrounding Val78 of human UHF1 protein.

该单克隆抗体是采用合成的与人源UHF12蛋白Val78残基周围序列相对应的肽段免疫动物而生产的。

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using UHRF1 (D6G8E) Rabbit mAb.Western blot方法检测不同细胞系的提取物,使用的抗体为 UHRF1 (D6G8E) Rabbit mAb。

IP

IP

Immunoprecipitation of UHRF1 from HeLa cell extracts, using Rabbit (DA1E) mAb IgG XP® Isotype Control #3900 (lane 2) or UHRF1 (D6G8E) Rabbit mAb (lane 3). Lane 1 is 10% input. Western blot analysis was performed using UHRF1 (D6G8E) Rabbit mAb.从 HeLa细胞提取物中免疫沉淀UHRF1,使用的抗体为Rabbit (DA1E) mAb IgG XP® Isotype Control #3900 (lane 2)或 UHRF1 (D6G8E) Rabbit mAb (lane 3)。Lane 1为10% input。 使用UHRF1 (D6G8E) Rabbit mAb进行Western blot检测。

Western Blotting

Western Blotting

Western blot analysis of extracts from HeLa cells, expressing either nontargeting shRNA (HeLa shNT) or shRNA targeting UHRF1 (HeLa shUHRF1), using UHRF1 (D6G8E) Rabbit mAb (upper) or GAPDH (D16H11) XP® Rabbit mAb #5174 (lower).Western blot方法检测表达nontargeting shRNA (HeLa shNT) 或 shRNA targeting UHRF1 (HeLa shUHRF1)的HeLa细胞,所用抗体为UHRF1 (D6G8E) Rabbit mAb (上图) 或 GAPDH (D16H11) XP® Rabbit mAb #5174 (下图)。

Background

Ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1), also known as Inverted CCAAT box-binding protein of 90 kDa (ICBP90) and Nuclear Zinc Finger Protein NP95 (NP95), is a nuclear protein that was first discovered as a CCAAT box-binding protein that regulates the expression of the Topoisomerase IIα and Rb1 genes (1,2). Later studies have shown that UHRF1 is required for maintenance of CpG DNA methylation, the process of copying pre-existing methylation patterns onto the newly synthesized DNA strand after DNA replication (3-5). UHRF1 localizes primarily with highly methylated pericentromeric heterochromatin and is required for proper structure and function of these regions of the genome (6,7). However, UHRF1 also localizes to euchromatic regions of the genome and functions to negatively regulate the expression of a subset of tumor suppressor genes (2,8,9). The localization and repressive functions of UHRF1 are both mediated by several protein domains, including a ubiquitin-like domain (UBQ), Tudor domain, PHD domain, SET and RING finger-associated (SRA) domain, and a RING finger domain. The SRA domain of UHRF1 binds with high affinity to hemi-methylated DNA and functions to properly target the associated maintenance DNA methyltransferase DNMT1 protein to mediate faithful methylation of the newly synthesized DNA strand (3-5). Additional targeting of UHRF1 to heterochromatin is mediated by the Tudor domain, which binds specifically to tri-methylated lysine 9 of histone H3, a histone mark associated with pericentromeric heterochromatin (10-12). Targeting of UHRF1 to euchromatin is further mediated by the PHD domain, which binds specifically to un-methylated arginine 2 of histone H3, which is commonly associated with euchromatin (13). In addition to recruiting DNMT1, UHRF1 recruits the histone deacetylase 1 (HDAC1) protein to target loci, resulting in deacetylation of histones, and providing an additional mechanism for transcriptional repression (3). Taken together, these studies demonstrate that UHRF1 functions to link DNA methylation and histone modifications to the maintenance of repressive chromatin structures. These functions of UHRF1 are important for proper maintenance of cell growth and proliferation, as research studies have shown UHRF1 over-expression in a number of cancers (breast, lung, colon, and prostate cancer) is associated with increased proliferation and malignancy (9,14-16).

Ubiquitin-like PHD and RING finger domain-containing protein 1 (UHRF1),也被称为Inverted CCAAT box-binding protein of 90 kDa (ICBP90)和Nuclear Zinc Finger Protein NP95 (NP95),是一个核蛋白,也是第一个被发现的能够调控拓扑异构酶IIα 和 Rb1基因的CCAAT box结合蛋白(1,2)。最近的研究表明UHRF1对于CpG DNA甲基化的维持以及DNA复制后将已有甲基化模式复制到新合成DNA 的过程所需要的(3-5)。UHRF1主要定位在高度甲基化的着丝粒异染色质,并且是基因组的这些区域正确的结构和功能所需要的(6,7)。但UHRF1同时还定位在基因组的常染色质区域,其功能是负调控肿瘤抑制基因的一个亚单位的表达(2,8,9)。UHRF1的定位和阻遏功能都是有几种蛋白结构域介导的,如ubiquitin-like domain (UBQ), Tudor domain, PHD domain, SET and RING finger-associated (SRA) domain,以及一个 RING finger domain。UHRF1的SRA结构域能够高亲和性的与半甲基化DNA结合,其功能是正确靶定相关的维持型DNA甲基转移酶 DNMT1蛋白从而介导新合成的DNA链的忠实甲基化(3-5)。UHRF1对异染色质的靶定是由Tudor结构域介导的,该结构域可特异性结合Lys9位点三甲基化的组蛋白H3,这是与着丝粒异染色质相关的一个组蛋白标记(10-12)。UHRF1靶定到常染色质是由PHD结构域进一步介导的,该结构域能特异性的集合到Arg2 为甲基化的组蛋白H3上,这个标志鲳鱼常染色体有关联(13)。除了招募DNMT1,UHRF1还能够募集histone deacetylase 1 (HDAC1)到目的基因座上,从而导致组蛋白的去乙酰化并为转录阻遏提供了另外一种机制(3)。综上所述,这些研究证明UHRF1的功能是将DNA甲基化和组蛋白修饰与阻遏染色质结构的维持联系起来。UHRF1的这些功能对于细胞生长和增殖的正常维持是非常重要的,研究发现UHRF1在许多肿瘤(乳腺、肺、结肠和前列腺癌)中的过表达与提高的增殖速度和恶性度有关(9,14-16)。

  1. Hopfner, R. et al. (2000) Cancer Res 60, 121-8.
  2. Jeanblanc, M. et al. (2005) Oncogene 24, 7337-45.
  3. Unoki, M. et al. (2004) Oncogene 23, 7601-10.
  4. Sharif, J. et al. (2007) Nature 450, 908-12.
  5. Bostick, M. et al. (2007) Science 317, 1760-4.
  6. Papait, R. et al. (2007) Mol Biol Cell 18, 1098-106.
  7. Papait, R. et al. (2008) Mol Biol Cell 19, 3554-63.
  8. Daskalos, A. et al. (2011) Cancer 117, 1027-37.
  9. Kim, J.K. et al. (2009) Nucleic Acids Res 37, 493-505.
  10. Nady, N. et al. (2011) J Biol Chem 286, 24300-11.
  11. Liu, X. et al. (2013) Nat Commun 4, 1563.
  12. Rothbart, S.B. et al. (2012) Nat Struct Mol Biol 19, 1155-60.
  13. Rajakumara, E. et al. (2011) Mol Cell 43, 275-84.
  14. Babbio, F. et al. (2012) Oncogene 31, 4878-87.
  15. Kofunato, Y. et al. (2012) Oncol Rep 28, 1997-2002.
  16. Unoki, M. et al. (2010) Br J Cancer 103, 217-22.

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