View source for 5i50


==Structure of OmoMYC bound to double-stranded DNA==
<StructureSection load='5i50' size='340' side='right'caption='[[5i50]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5i50]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I50 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I50 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.701&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5i50 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i50 OCA], [https://pdbe.org/5i50 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i50 RCSB], [https://www.ebi.ac.uk/pdbsum/5i50 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i50 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors.  Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1.  Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:[https://omim.org/entry/113970 113970]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
== Function ==
[https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.
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== Publication Abstract from PubMed ==
MYC genes have both essential roles during normal development and exert oncogenic functions during tumorigenesis. Expression of a dominant-negative allele of MYC, termed OmoMYC, can induce rapid tumor regression in mouse models with little toxicity for normal tissues. How OmoMYC discriminates between physiological and oncogenic functions of MYC is unclear. We have solved the crystal structure of OmoMYC and show that it forms a stable homodimer and as such recognizes DNA in the same manner as the MYC/MAX heterodimer. OmoMYC attenuates both MYC-dependent activation and repression by competing with MYC/MAX for binding to chromatin, effectively lowering MYC/MAX occupancy at its cognate binding sites. OmoMYC causes the largest decreases in promoter occupancy and changes in expression on genes that are invaded by oncogenic MYC levels. A signature of OmoMYC-regulated genes defines subgroups with high MYC levels in multiple tumor entities and identifies novel targets for the eradication of MYC-driven tumors.Oncogene advance online publication, 17 October 2016; doi:10.1038/onc.2016.354.

OmoMYC blunts promoter invasion by oncogenic MYC to inhibit gene expression characteristic of MYC-dependent tumors.,Jung LA, Gebhardt A, Koelmel W, Ade CP, Walz S, Kuper J, von Eyss B, Letschert S, Redel C, d'Artista L, Biankin A, Zender L, Sauer M, Wolf E, Evan G, Kisker C, Eilers M Oncogene. 2016 Oct 17. doi: 10.1038/onc.2016.354. PMID:27748763<ref>PMID:27748763</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5i50" style="background-color:#fffaf0;"></div>

==See Also==
*[[C-Myc|C-Myc]]
*[[Stathmin-4 3D structures|Stathmin-4 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Eilers M]]
[[Category: Jung LA]]
[[Category: Kisker C]]
[[Category: Koelmel W]]
[[Category: Kuper J]]