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2mjv

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{{STRUCTURE_2mjv| PDB=2mjv | SCENE= }}
 
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===Solution structures of second bromodomain of Brd4 with di-acetylated Twist peptide===
 
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{{ABSTRACT_PUBMED_24525235}}
 
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==Disease==
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==Solution structures of second bromodomain of Brd4 with di-acetylated Twist peptide==
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[[http://www.uniprot.org/uniprot/TWST1_HUMAN TWST1_HUMAN]] Isolated scaphocephaly;Isolated brachycephaly;Saethre-Chotzen syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Note=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.<ref>PMID:12543779</ref> <ref>PMID:11733348</ref>
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<StructureSection load='2mjv' size='340' side='right'caption='[[2mjv]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2mjv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MJV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MJV FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ALY:N(6)-ACETYLLYSINE'>ALY</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mjv OCA], [https://pdbe.org/2mjv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mjv RCSB], [https://www.ebi.ac.uk/pdbsum/2mjv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mjv ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/TWST1_HUMAN TWST1_HUMAN] Isolated scaphocephaly;Isolated brachycephaly;Saethre-Chotzen syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
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== Function ==
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[https://www.uniprot.org/uniprot/TWST1_HUMAN TWST1_HUMAN] Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation.<ref>PMID:12553906</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we report a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a "histone H4-mimic" GK-X-GK motif that is diacetylated by Tip60. The diacetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructing an activated Twist/BRD4/P-TEFb/RNA-Pol II complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.
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==Function==
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Disrupting the Interaction of BRD4 with Diacetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer.,Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, Lin Y, Li J, Kang T, Tao M, Rusinova E, Zhang G, Wang C, Zhu H, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BP Cancer Cell. 2014 Feb 10;25(2):210-25. doi: 10.1016/j.ccr.2014.01.028. PMID:24525235<ref>PMID:24525235</ref>
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[[http://www.uniprot.org/uniprot/TWST1_HUMAN TWST1_HUMAN]] Acts as a transcriptional regulator. Inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. This interaction probably involves the basic domains of both proteins. Also represses expression of proinflammatory cytokines such as TNFA and IL1B. Regulates cranial suture patterning and fusion. Activates transcription as a heterodimer with E proteins. Regulates gene expression differentially, depending on dimer composition. Homodimers induce expression of FGFR2 and POSTN while heterodimers repress FGFR2 and POSTN expression and induce THBS1 expression. Heterodimerization is also required for osteoblast differentiation.<ref>PMID:12553906</ref> [[http://www.uniprot.org/uniprot/BRD4_HUMAN BRD4_HUMAN]] Plays a role in a process governing chromosomal dynamics during mitosis (By similarity).
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2mjv]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MJV OCA].
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</div>
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<div class="pdbe-citations 2mjv" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:024525235</ref><references group="xtra"/><references/>
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*[[Bromodomain-containing protein 3D structures|Bromodomain-containing protein 3D structures]]
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[[Category: Zeng, L.]]
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== References ==
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[[Category: Zhou, M.]]
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<references/>
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[[Category: Transcription]]
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__TOC__
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[[Category: Tumorigenesis]]
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Zeng L]]
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[[Category: Zhou M]]

Current revision

Solution structures of second bromodomain of Brd4 with di-acetylated Twist peptide

PDB ID 2mjv

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