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PDP - Template Name: Antibody Sampler Kit
PDP - Template ID: *******4a3ef3a
  1. Products /
  2. Primary Antibodies /
  3. BRD4 Antibody Sampler Kit

BRD4 Antibody Sampler Kit #82970

    Product Information

    Kit Usage Information

    Protocols

    Product Description

    The BRD4 Antibody Sampler Kit provides an economical means of detecting various BRD4 isoforms. The kit includes enough antibodies to perform two western blot experiments with each primary antibody.

    Background

    Bromodomain-containing protein 4 (BRD4) is a member of the bromodomains and extra terminal (BET) family of proteins, which also includes BRD2, BRD3, and BRDT (1-3). BET family proteins contain two tandem bromodomains and an extra terminal (ET) domain, and bind acetyl lysine residues (3). BRD4 is a chromatin-binding protein with a preference for Lys14 on histone H3 as well as Lys5 and Lys12 on histone H4 (4). BRD4 chromatin binding occurs throughout the cell cycle, including condensed mitotic chromosomes, when the majority of genes are silenced (5). BRD4 association with chromatin during mitosis is thought to be an important part of the bookmarking mechanism to accelerate reactivation of the silenced genes upon exit from mitosis (2,6). BRD4 has been shown to facilitate transcription by recruiting the positive transcription elongation factor b (pTEFb) complex that phosphorylates Ser2 of the heptapeptide repeat of the carboxy-terminal domain of RNA polymerase II, promoting transcription elongation (3,7,8). In addition, BRD4 has been found to be part of the super elongation complex and the polymerase associated factor complex (PAFc) in MLL-fusion derived leukemia cell lines, demonstrating a role for BRD4 in the regulation of transcription elongation (9). Research studies have shown that BRD4 (and BET family proteins) may be promising therapeutic targets for various Myc-driven cancers, such as Burkitt’s lymphoma and certain acute myeloid leukemias (1,10,11). Investigators have found molecular inhibition of BET proteins to be effective in inducing apoptosis in various MLL-fusion driven leukemic cell lines by competing BRD3 and BRD4 from chromatin, leading to reduced expression of Bcl-2, Myc, and CDK6 (9). BET inhibition has also been shown to have antitumor activities against nuclear protein in testis (NUT) midline carcinoma cell lines and xenografts in mice where BRD4 is found to be a frequent translocation partner of the NUT protein (12). In addition, BRD4 regulates the expression of some inflammatory genes, and inhibition of BRD4 (and BET family proteins) chromatin binding causes reduced expression of a subset of inflammatory genes in macrophages, leading to protection against endotoxic shock and sepsis (13).

    The expression of BRD4 isoform C, also known as the short isoform (BRD4-S), is similar to the long isoform (BRD4-L). The balance of expression between the two isoforms has been shown to contribute to disease states, where BRD4-S has shown to be oncogenic in a few contexts (14-16). BRD4-S is the predominant isoform that binds to modified histones and has a stronger affinity than BRD4-L (17,18). BRD4-S also plays a role in DNA damage, where it recruits the condensin II complex to enhance DNA damage induced cell death (18).
    1. Belkina, A.C. and Denis, G.V. (2012) Nat Rev Cancer 12, 465-77.
    2. Voigt, P. and Reinberg, D. (2011) Genome Biol 12, 133.
    3. Wu, S.Y. and Chiang, C.M. (2007) J Biol Chem 282, 13141-5.
    4. Dey, A. et al. (2003) Proc Natl Acad Sci U S A 100, 8758-63.
    5. Dey, A. et al. (2009) Mol Biol Cell 20, 4899-909.
    6. Zhao, R. et al. (2011) Nat Cell Biol 13, 1295-304.
    7. Jang, M.K. et al. (2005) Mol Cell 19, 523-34.
    8. Yang, Z. et al. (2005) Mol Cell 19, 535-45.
    9. Dawson, M.A. et al. (2011) Nature 478, 529-33.
    10. Muller, S. et al. (2011) Expert Rev Mol Med 13, e29.
    11. Mertz, J.A. et al. (2011) Proc Natl Acad Sci U S A 108, 16669-74.
    12. Filippakopoulos, P. et al. (2010) Nature 468, 1067-73.
    13. Nicodeme, E. et al. (2010) Nature 468, 1119-23.
    14. Wu, S.Y. et al. (2020) Mol Cell 78, 1114-1132.e10.
    15. Crawford, N.P. et al. (2008) Proc Natl Acad Sci USA 105, 6380-5.
    16. Fernandez, P. et al. (2014) Cell Rep 9, 248-260.
    17. Wang, R. et al. (2012) J Biol Chem 287, 10738-52.
    18. Han, X. et al. (2020) Nat Struct Mol Biol 27, 333-341.

    Database Links

    UniProt ID: O60885-3 , O60885 , O60885-2


    Entrez-Gene Id: 23476


    限制使用

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    For Research Use Only. Not For Use In Diagnostic Procedures.
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