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| | ==Crystal structure of a complex of the Miz1- and Nac1 POZ domains.== | | ==Crystal structure of a complex of the Miz1- and Nac1 POZ domains.== |
| - | <StructureSection load='4u2n' size='340' side='right' caption='[[4u2n]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4u2n' size='340' side='right'caption='[[4u2n]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4u2n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U2N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U2N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4u2n]] is a 2 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=4U2N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4U2N FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4u2m|4u2m]]</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]] 2.3Å</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=4u2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u2n RCSB], [http://www.ebi.ac.uk/pdbsum/4u2n 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=4u2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u2n OCA], [https://pdbe.org/4u2n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4u2n RCSB], [https://www.ebi.ac.uk/pdbsum/4u2n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4u2n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == 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/NACC1_HUMAN NACC1_HUMAN] Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines.<ref>PMID:17130457</ref> <ref>PMID:17804717</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 4u2n" style="background-color:#fffaf0;"></div> |
| | == 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
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] NACC1_HUMAN Functions as a transcriptional repressor. Seems to function as a transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4. Contributes to tumor progression, and tumor cell proliferation and survival. This may be mediated at least in part through repressing transcriptional activity of GADD45GIP1. Required for recruiting the proteasome from the nucleus to the cytoplasm and dendritic spines.[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.
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
- ↑ Nakayama K, Nakayama N, Davidson B, Sheu JJ, Jinawath N, Santillan A, Salani R, Bristow RE, Morin PJ, Kurman RJ, Wang TL, Shih IeM. A BTB/POZ protein, NAC-1, is related to tumor recurrence and is essential for tumor growth and survival. Proc Natl Acad Sci U S A. 2006 Dec 5;103(49):18739-44. Epub 2006 Nov 27. PMID:17130457 doi:http://dx.doi.org/0604083103
- ↑ Nakayama K, Nakayama N, Wang TL, Shih IeM. NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor. Cancer Res. 2007 Sep 1;67(17):8058-64. PMID:17804717 doi:http://dx.doi.org/10.1158/0008-5472.CAN-07-1357
- ↑ 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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