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| | <StructureSection load='4yyp' size='340' side='right'caption='[[4yyp]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='4yyp' size='340' side='right'caption='[[4yyp]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yyp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YYP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YYP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yyp]] 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=4YYP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YYP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 2.6Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n15|2n15]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLK4, SAK, STK18 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4yyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yyp OCA], [https://pdbe.org/4yyp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yyp RCSB], [https://www.ebi.ac.uk/pdbsum/4yyp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yyp ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Polo_kinase Polo kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.21 2.7.11.21] </span></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=4yyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yyp OCA], [http://pdbe.org/4yyp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yyp RCSB], [http://www.ebi.ac.uk/pdbsum/4yyp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yyp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/STIL_HUMAN STIL_HUMAN]] Precursor T-cell acute lymphoblastic leukemia;Autosomal recessive primary microcephaly. A chromosomal aberration involving STIL may be a cause of some T-cell acute lymphoblastic leukemias (T-ALL). A deletion at 1p32 between STIL and TAL1 genes leads to STIL/TAL1 fusion mRNA with STIL exon 1 slicing to TAL1 exon 3. As both STIL exon 1 and TAL1 exon 3 are 5'-untranslated exons, STIL/TAL1 fusion mRNA predicts a full length TAL1 protein under the control of the STIL promoter, leading to inappropriate TAL1 expression. In childhood T-cell malignancies (T-ALL), a type of defect such as STIL/TAL1 fusion is associated with a good prognosis. In cultured lymphocytes from healthy adults, STIL/TAL1 fusion mRNA may be detected after 7 days of culture. The disease is caused by mutations affecting the gene represented in this entry. | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLK4_HUMAN PLK4_HUMAN]] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref> [[http://www.uniprot.org/uniprot/STIL_HUMAN STIL_HUMAN]] Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1.<ref>PMID:16024801</ref> <ref>PMID:9372240</ref> | + | [https://www.uniprot.org/uniprot/PLK4_HUMAN PLK4_HUMAN] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.<ref>PMID:16326102</ref> <ref>PMID:16244668</ref> <ref>PMID:17681131</ref> <ref>PMID:18239451</ref> <ref>PMID:19164942</ref> <ref>PMID:21725316</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein kinase|Serine/threonine protein kinase]] | + | *[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Polo kinase]]
| + | [[Category: Arquint C]] |
| - | [[Category: Arquint, C]] | + | [[Category: Boehm R]] |
| - | [[Category: Boehm, R]] | + | [[Category: Gabryjonczyk A]] |
| - | [[Category: Gabryjonczyk, A]] | + | [[Category: Hiller S]] |
| - | [[Category: Hiller, S]] | + | [[Category: Imseng S]] |
| - | [[Category: Imseng, S]] | + | [[Category: Maier T]] |
| - | [[Category: Maier, T]] | + | [[Category: Nigg EA]] |
| - | [[Category: Nigg, E A]] | + | [[Category: Sauer E]] |
| - | [[Category: Sauer, E]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Polo-box]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
PLK4_HUMAN Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.
STIL binding to Polo-box 3 of PLK4 regulates centriole duplication.,Arquint C, Gabryjonczyk AM, Imseng S, Bohm R, Sauer E, Hiller S, Nigg EA, Maier T Elife. 2015 Jul 18;4. doi: 10.7554/eLife.07888. PMID:26188084[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005 Dec 20;15(24):2199-207. Epub 2005 Dec 1. PMID:16326102 doi:http://dx.doi.org/10.1016/j.cub.2005.11.042
- ↑ Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005 Nov;7(11):1140-6. PMID:16244668 doi:http://dx.doi.org/10.1038/ncb1320
- ↑ Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002
- ↑ Bonni S, Ganuelas ML, Petrinac S, Hudson JW. Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008 Feb 15;7(4):545-7. Epub 2007 Nov 25. PMID:18239451
- ↑ Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW. Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. PMID:19164942
- ↑ Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP, Hoffmann I, Gonczy P, Malek NP. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011 Jul 3;13(8):1004-9. doi: 10.1038/ncb2282. PMID:21725316 doi:http://dx.doi.org/10.1038/ncb2282
- ↑ Arquint C, Gabryjonczyk AM, Imseng S, Bohm R, Sauer E, Hiller S, Nigg EA, Maier T. STIL binding to Polo-box 3 of PLK4 regulates centriole duplication. Elife. 2015 Jul 18;4. doi: 10.7554/eLife.07888. PMID:26188084 doi:http://dx.doi.org/10.7554/eLife.07888
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