5uy9
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Prolyl isomerase Pin1 R14A mutant bound with Brd4 peptide== | |
| + | <StructureSection load='5uy9' size='340' side='right'caption='[[5uy9]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5uy9]] 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=5UY9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UY9 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]] 1.85Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NIT:4-NITROANILINE'>NIT</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=5uy9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uy9 OCA], [https://pdbe.org/5uy9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uy9 RCSB], [https://www.ebi.ac.uk/pdbsum/5uy9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uy9 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PIN1_HUMAN PIN1_HUMAN] Essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity. Displays a preference for an acidic residue N-terminal to the isomerized proline bond. Catalyzes pSer/Thr-Pro cis/trans isomerizations. Down-regulates kinase activity of BTK. Can transactivate multiple oncogenes and induce centrosome amplification, chromosome instability and cell transformation. Required for the efficient dephosphorylation and recycling of RAF1 after mitogen activation.<ref>PMID:15664191</ref> <ref>PMID:16644721</ref> <ref>PMID:21497122</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | BRD4 has emerged as an important factor in tumorigenesis by promoting the transcription of genes involved in cancer development. However, how BRD4 is regulated in cancer cells remains largely unknown. Here, we report that the stability and functions of BRD4 are positively regulated by prolyl isomerase PIN1 in gastric cancer cells. PIN1 directly binds to phosphorylated threonine (T) 204 of BRD4 as revealed by peptide binding and crystallographic studies and enhances BRD4's stability by inhibiting its ubiquitination. PIN1 also catalyses the isomerization of proline 205 of BRD4 and induces its conformational change, which promotes its interaction with CDK9 and increases BRD4's transcriptional activity. Substitution of BRD4 with PIN1-binding-defective BRD4-T204A mutant in gastric cancer cells reduces BRD4's stability, attenuates BRD4-mediated gene expression by impairing its interaction with CDK9 and suppresses gastric cancer cell proliferation, migration and invasion, and tumor formation. Our results identify BRD4 as a new target of PIN1 and suggest that interfering with their interaction could be a potential therapeutic approach for cancer treatment.Oncogene advance online publication, 8 May 2017; doi:10.1038/onc.2017.137. | ||
| - | + | Prolyl isomerase PIN1 regulates the stability, transcriptional activity and oncogenic potential of BRD4.,Hu X, Dong SH, Chen J, Zhou XZ, Chen R, Nair S, Lu KP, Chen LF Oncogene. 2017 May 8. doi: 10.1038/onc.2017.137. PMID:28481868<ref>PMID:28481868</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Dong | + | <div class="pdbe-citations 5uy9" style="background-color:#fffaf0;"></div> |
| - | [[Category: Nair | + | |
| + | ==See Also== | ||
| + | *[[Peptidyl-prolyl cis-trans isomerase 3D structures|Peptidyl-prolyl cis-trans isomerase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dong S-H]] | ||
| + | [[Category: Nair S]] | ||
Current revision
Prolyl isomerase Pin1 R14A mutant bound with Brd4 peptide
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