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| | ==Crystal structure of a complex of the Miz1- and BCL6 POZ domains.== | | ==Crystal structure of a complex of the Miz1- and BCL6 POZ domains.== |
| - | <StructureSection load='4u2m' size='340' side='right' caption='[[4u2m]], [[Resolution|resolution]] 2.23Å' scene=''> | + | <StructureSection load='4u2m' size='340' side='right'caption='[[4u2m]], [[Resolution|resolution]] 2.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u2m]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U2M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U2M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u2m]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U2M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U2M FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u2n|4u2n]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.23Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4u2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u2m RCSB], [http://www.ebi.ac.uk/pdbsum/4u2m PDBsum]</span></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=4u2m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2m OCA], [https://pdbe.org/4u2m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u2m RCSB], [https://www.ebi.ac.uk/pdbsum/4u2m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u2m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ZBT17_HUMAN ZBT17_HUMAN]] Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.<ref>PMID:9312026</ref> <ref>PMID:9308237</ref> <ref>PMID:19164764</ref> | + | [https://www.uniprot.org/uniprot/ZBT17_HUMAN ZBT17_HUMAN] Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.<ref>PMID:9312026</ref> <ref>PMID:9308237</ref> <ref>PMID:19164764</ref> [https://www.uniprot.org/uniprot/BCL6_HUMAN BCL6_HUMAN] Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.<ref>PMID:9649500</ref> <ref>PMID:18280243</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4u2m" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Stead, M A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Wright, S C]] | + | [[Category: Large Structures]] |
| - | [[Category: Btb domain]] | + | [[Category: Stead MA]] |
| - | [[Category: Poz domain]] | + | [[Category: Wright SC]] |
| - | [[Category: Transcription]]
| + | |
| Structural highlights
Disease
BCL6_HUMAN Note=Chromosomal aberrations involving BCL6 may be a cause of B-cell non-Hodgkin lymphoma. Translocation t(3;14)(q27;q32); translocation t(3;22)(q27;q11) with immunoglobulin gene regions. Note=A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1. Note=A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
Function
ZBT17_HUMAN Plays a critical role in early lymphocyte development, where it is essential to prevent apoptosis in lymphoid precursors, allowing them to survive in response to IL7 and undergo proper lineage commitment (By similarity). Transcription factor that can function as an activator or repressor depending on its binding partners, and by targeting negative regulators of cell cycle progression. Has been shown to bind to the promoters of adenovirus major late protein and cyclin D1 and activate transcription. Required for early embryonic development during gastrulation.[1] [2] [3] BCL6_HUMAN Transcriptional repressor which is required for germinal center formation and antibody affinity maturation. Probably plays an important role in lymphomagenesis.[4] [5]
Publication Abstract from PubMed
The POZ domain is an evolutionarily conserved protein-protein interaction domain that is found in approximately 40 mammalian transcription factors. POZ domains mediate both homodimerization and the heteromeric interactions of different POZ-domain transcription factors with each other. Miz1 is a POZ-domain transcription factor that regulates cell-cycle arrest and DNA-damage responses. The activities of Miz1 are altered by its interaction with the POZ-domain transcriptional repressors BCL6 and NAC1, and these interactions have been implicated in tumourigenesis in B-cell lymphomas and in ovarian serous carcinomas that overexpress BCL6 and NAC1, respectively. A strategy for the purification of tethered POZ domains that form forced heterodimers is described, and crystal structures of the heterodimeric POZ domains of Miz1/BCL6 and of Miz1/NAC1 are reported. These structures will be relevant for the design of therapeutics that target POZ-domain interaction interfaces.
Structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1.,Stead MA, Wright SC Acta Crystallogr F Struct Biol Commun. 2014 Dec 1;70(Pt 12):1591-6. doi:, 10.1107/S2053230X14023449. Epub 2014 Nov 14. PMID:25484205[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Peukert K, Staller P, Schneider A, Carmichael G, Hanel F, Eilers M. An alternative pathway for gene regulation by Myc. EMBO J. 1997 Sep 15;16(18):5672-86. PMID:9312026 doi:10.1093/emboj/16.18.5672
- ↑ Schneider A, Peukert K, Eilers M, Hanel F. Association of Myc with the zinc-finger protein Miz-1 defines a novel pathway for gene regulation by Myc. Curr Top Microbiol Immunol. 1997;224:137-46. PMID:9308237
- ↑ Basu S, Liu Q, Qiu Y, Dong F. Gfi-1 represses CDKN2B encoding p15INK4B through interaction with Miz-1. Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1433-8. doi: 10.1073/pnas.0804863106., Epub 2009 Jan 22. PMID:19164764 doi:10.1073/pnas.0804863106
- ↑ Niu H, Ye BH, Dalla-Favera R. Antigen receptor signaling induces MAP kinase-mediated phosphorylation and degradation of the BCL-6 transcription factor. Genes Dev. 1998 Jul 1;12(13):1953-61. PMID:9649500
- ↑ Ghetu AF, Corcoran CM, Cerchietti L, Bardwell VJ, Melnick A, Prive GG. Structure of a BCOR corepressor peptide in complex with the BCL6 BTB domain dimer. Mol Cell. 2008 Feb 15;29(3):384-91. PMID:18280243 doi:10.1016/j.molcel.2007.12.026
- ↑ Stead MA, Wright SC. Structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1. Acta Crystallogr F Struct Biol Commun. 2014 Dec 1;70(Pt 12):1591-6. doi:, 10.1107/S2053230X14023449. Epub 2014 Nov 14. PMID:25484205 doi:http://dx.doi.org/10.1107/S2053230X14023449
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