8j9a
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Solution structure of ABD3 (residues 453-561) of human MED15 isoform 2== | |
| + | <StructureSection load='8j9a' size='340' side='right'caption='[[8j9a]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8j9a]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8J9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J9A FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=8j9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j9a OCA], [https://pdbe.org/8j9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j9a RCSB], [https://www.ebi.ac.uk/pdbsum/8j9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j9a ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MED15_HUMAN MED15_HUMAN] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway.<ref>PMID:12167862</ref> <ref>PMID:16630888</ref> <ref>PMID:16799563</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) play key roles in cancers through transcriptional outputs. However, their transactivation mechanisms remain unclear, and effective targeting strategies are lacking. Here, we show that YAP/TAZ possess a hydrophobic transactivation domain (TAD). TAD knockout prevents tumor establishment due to growth defects and enhances immune attack. Mechanistically, TADs facilitate preinitiation complex (PIC) assembly by recruiting the TATA-binding protein-associated factor 4 (TAF4)-dependent TFIID complex and enhance RNA polymerase II (Pol II) elongation through mediator complex subunit 15 (MED15)-dependent mediator recruitment for the expressions of oncogenic/immune-suppressive programs. The synthesized peptide TJ-M11 selectively disrupts TAD interactions with MED15 and TAF4, suppressing tumor growth and sensitizing tumors to immunotherapy. Our findings demonstrate that YAP/TAZ TADs exhibit dual functions in PIC assembly and Pol II elongation via hydrophobic interactions, which represent actionable targets for cancer therapy and combination immunotherapy. | ||
| - | + | The mechanism of YAP/TAZ transactivation and dual targeting for cancer therapy.,Yu M, Wang J, Zhang X, Zhang H, Li C, Li J, Lin J, Zheng J, Huang L, Li Y, Sun S Nat Commun. 2025 Apr 24;16(1):3855. doi: 10.1038/s41467-025-59309-w. PMID:40274828<ref>PMID:40274828</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 8j9a" style="background-color:#fffaf0;"></div> |
| - | [[Category: Li | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Li Y]] | ||
| + | [[Category: Zhang H]] | ||
Current revision
Solution structure of ABD3 (residues 453-561) of human MED15 isoform 2
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