Bromodomain Containing Protein 4 (BRD4)

CAP; HUNKI; MCAP; HUNK1; Chromosome-Associated Protein

SPN	R673
HGNC	13575
MGI	1888520
PubMed	23728299
RGD	1307282
UniProt	O60885
Wiki	BRD4

Bromodomain-containing protein 4 is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described.A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUT which produces a BRD4-NUT fusion protein.

Reference

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Am. J. Pathol. 159:1987-1992(2001) [PubMed] [Europe PMC] [Abstract]

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Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"BRD4-NUT fusion oncogene: a novel mechanism in aggressive carcinoma."
Cancer Res. 63:304-307(2003) [PubMed] [Europe PMC] [Abstract]

"The bromodomain protein Brd4 is a positive regulatory component of P-TEFb and stimulates RNA polymerase II-dependent transcription."
Mol. Cell 19:523-534(2005) [PubMed] [Europe PMC] [Abstract]

"Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4."
Mol. Cell 19:535-545(2005) [PubMed] [Europe PMC] [Abstract]

"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]

"Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen interacts with bromodomain protein Brd4 on host mitotic chromosomes."
J. Virol. 80:8909-8919(2006) [PubMed] [Europe PMC] [Abstract]

"ChlR1 is required for loading papillomavirus E2 onto mitotic chromosomes and viral genome maintenance."
Mol. Cell 24:867-876(2006) [PubMed] [Europe PMC] [Abstract]

"The EBNA1 protein of Epstein-Barr virus functionally interacts with Brd4."
J. Virol. 82:12009-12019(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Control of inducible gene expression by signal-dependent transcriptional elongation."
Cell 138:129-145(2009) [PubMed] [Europe PMC] [Abstract]

"Brd4 coactivates transcriptional activation of NF-kappaB via specific binding to acetylated RelA."
Mol. Cell. Biol. 29:1375-1387(2009) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

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Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3."
Mol. Cell. Biol. 31:2641-2652(2011) [PubMed] [Europe PMC] [Abstract]

"Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin targeting to transcriptional regulation."
Nucleic Acids Res. 39:9592-9604(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Bromodomain protein Brd4 associated with acetylated chromatin is important for maintenance of higher-order chromatin structure."
J. Biol. Chem. 287:10738-10752(2012) [PubMed] [Europe PMC] [Abstract]

"Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells."
J. Biol. Chem. 287:43137-43155(2012) [PubMed] [Europe PMC] [Abstract]

"BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain."
Proc. Natl. Acad. Sci. U.S.A. 109:6927-6932(2012) [PubMed] [Europe PMC] [Abstract]

"Phospho switch triggers Brd4 chromatin binding and activator recruitment for gene-specific targeting."
Mol. Cell 49:843-857(2013) [PubMed] [Europe PMC] [Abstract]

"BRD4 coordinates recruitment of pause release factor P-TEFb and the pausing complex NELF/DSIF to regulate transcription elongation of interferon-stimulated genes."
Mol. Cell. Biol. 33:2497-2507(2013) [PubMed] [Europe PMC] [Abstract]

"The bromodomain protein Brd4 insulates chromatin from DNA damage signalling."
Nature 498:246-250(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"Structural basis and binding properties of the second bromodomain of Brd4 with acetylated histone tails."
Biochemistry 47:6403-6417(2008) [PubMed] [Europe PMC] [Abstract]

"Selective inhibition of BET bromodomains."
Nature 468:1067-1073(2010) [PubMed] [Europe PMC] [Abstract]

"Suppression of inflammation by a synthetic histone mimic."
Nature 468:1119-1123(2010) [PubMed] [Europe PMC] [Abstract]

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Nature 478:529-533(2011) [PubMed] [Europe PMC] [Abstract]

"Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family."
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"Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition."
J. Biol. Chem. 287:28840-28851(2012) [PubMed] [Europe PMC] [Abstract]

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J. Med. Chem. 55:576-586(2012) [PubMed] [Europe PMC] [Abstract]

"Identification of a chemical probe for bromo and extra C-terminal bromodomain inhibition through optimization of a fragment-derived hit."
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"Histone recognition and large-scale structural analysis of the human bromodomain family."
Cell 149:214-231(2012) [PubMed] [Europe PMC] [Abstract]

"Optimization of 3,5-dimethylisoxazole derivatives as potent bromodomain ligands."
J. Med. Chem. 56:3217-3227(2013) [PubMed] [Europe PMC] [Abstract]

"Fragment-based drug discovery of 2-thiazolidinones as inhibitors of the histone reader BRD4 bromodomain."
J. Med. Chem. 56:3833-3851(2013) [PubMed] [Europe PMC] [Abstract]