5wzz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The | + | ==The SIAH E3 ubiquitin ligases promote Wnt/ beta-catenin signaling through mediating Wnt-induced Axin degradation== |
| + | <StructureSection load='5wzz' size='340' side='right'caption='[[5wzz]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5wzz]] is a 8 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=5WZZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WZZ 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]] 2.103Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5wzz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wzz OCA], [https://pdbe.org/5wzz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wzz RCSB], [https://www.ebi.ac.uk/pdbsum/5wzz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wzz ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SIAH1_HUMAN SIAH1_HUMAN] E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins.<ref>PMID:9334332</ref> <ref>PMID:9858595</ref> <ref>PMID:11146551</ref> <ref>PMID:10747903</ref> <ref>PMID:11389839</ref> <ref>PMID:11389840</ref> <ref>PMID:11483517</ref> <ref>PMID:11483518</ref> <ref>PMID:11752454</ref> <ref>PMID:12072443</ref> <ref>PMID:14506261</ref> <ref>PMID:14654780</ref> <ref>PMID:14645235</ref> <ref>PMID:15064394</ref> <ref>PMID:18536714</ref> <ref>PMID:19224863</ref> <ref>PMID:20508617</ref> <ref>PMID:22483617</ref> <ref>PMID:16085652</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Wnt/beta-catenin signaling pathway plays essential roles in embryonic development and adult tissue homeostasis. Axin is a concentration-limiting factor responsible for the formation of the beta-catenin destruction complex. Wnt signaling itself promotes the degradation of Axin. However, the underlying molecular mechanism and biological relevance of this targeting of Axin have not been elucidated. Here, we identify SIAH1/2 (SIAH) as the E3 ligase mediating Wnt-induced Axin degradation. SIAH proteins promote the ubiquitination and proteasomal degradation of Axin through interacting with a VxP motif in the GSK3-binding domain of Axin, and this function of SIAH is counteracted by GSK3 binding to Axin. Structural analysis reveals that the Axin segment responsible for SIAH binding is also involved in GSK3 binding but adopts distinct conformations in Axin/SIAH and Axin/GSK3 complexes. Knockout of SIAH1 blocks Wnt-induced Axin ubiquitination and attenuates Wnt-induced beta-catenin stabilization. Our data suggest that Wnt-induced dissociation of the Axin/GSK3 complex allows SIAH to interact with Axin not associated with GSK3 and promote its degradation and that SIAH-mediated Axin degradation represents an important feed-forward mechanism to achieve sustained Wnt/beta-catenin signaling. | ||
| - | + | The SIAH E3 ubiquitin ligases promote Wnt/beta-catenin signaling through mediating Wnt-induced Axin degradation.,Ji L, Jiang B, Jiang X, Charlat O, Chen A, Mickanin C, Bauer A, Xu W, Yan X, Cong F Genes Dev. 2017 May 1;31(9):904-915. doi: 10.1101/gad.300053.117. Epub 2017 May, 25. PMID:28546513<ref>PMID:28546513</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5wzz" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bauer A]] | ||
| + | [[Category: Charlat O]] | ||
| + | [[Category: Chen A]] | ||
| + | [[Category: Cong F]] | ||
| + | [[Category: Ji L]] | ||
| + | [[Category: Jiang B]] | ||
| + | [[Category: Jiang X]] | ||
| + | [[Category: Mickanin C]] | ||
| + | [[Category: Xu W]] | ||
| + | [[Category: Yan X-X]] | ||
Current revision
The SIAH E3 ubiquitin ligases promote Wnt/ beta-catenin signaling through mediating Wnt-induced Axin degradation
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Categories: Homo sapiens | Large Structures | Bauer A | Charlat O | Chen A | Cong F | Ji L | Jiang B | Jiang X | Mickanin C | Xu W | Yan X-X
