2l9m
From Proteopedia
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==Structure of cIAP1 CARD== | ==Structure of cIAP1 CARD== | ||
| - | <StructureSection load='2l9m' size='340' side='right' caption='[[2l9m | + | <StructureSection load='2l9m' size='340' side='right'caption='[[2l9m]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[2l9m]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2l9m]] 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=2L9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L9M FirstGlance]. <br> |
| - | <b> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l9m OCA], [https://pdbe.org/2l9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l9m RCSB], [https://www.ebi.ac.uk/pdbsum/2l9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l9m ProSAT]</span></td></tr> |
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/BIRC2_HUMAN BIRC2_HUMAN] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.<ref>PMID:15665297</ref> <ref>PMID:18082613</ref> <ref>PMID:21145488</ref> <ref>PMID:21653699</ref> <ref>PMID:21931591</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
E3 ligases mediate the covalent attachment of ubiquitin to target proteins thereby enabling ubiquitin-dependent signaling. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Cellular inhibitor of apoptosis (cIAP) proteins are E3 ligases that modulate diverse biological processes such as cell survival, proliferation, and migration. Here, we have solved the structure of the caspase recruitment domain (CARD) of cIAP1 and identified that it is required for cIAP1 autoregulation. We demonstrate that the CARD inhibits activation of cIAP1's E3 activity by preventing RING dimerization, E2 binding, and E2 activation. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Further, CARD-mediated autoregulation is also necessary to maximally suppress caspase-8-dependent apoptosis and vascular tree degeneration in vivo. Taken together, our data reveal mechanisms by which the E3 ligase activity of cIAP1 is controlled, and how its deregulation impacts on cell proliferation, migration and cell survival. | E3 ligases mediate the covalent attachment of ubiquitin to target proteins thereby enabling ubiquitin-dependent signaling. Unraveling how E3 ligases are regulated is important because miscontrolled ubiquitylation can lead to disease. Cellular inhibitor of apoptosis (cIAP) proteins are E3 ligases that modulate diverse biological processes such as cell survival, proliferation, and migration. Here, we have solved the structure of the caspase recruitment domain (CARD) of cIAP1 and identified that it is required for cIAP1 autoregulation. We demonstrate that the CARD inhibits activation of cIAP1's E3 activity by preventing RING dimerization, E2 binding, and E2 activation. Moreover, we show that the CARD is required to suppress cell proliferation and migration. Further, CARD-mediated autoregulation is also necessary to maximally suppress caspase-8-dependent apoptosis and vascular tree degeneration in vivo. Taken together, our data reveal mechanisms by which the E3 ligase activity of cIAP1 is controlled, and how its deregulation impacts on cell proliferation, migration and cell survival. | ||
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CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration.,Lopez J, John SW, Tenev T, Rautureau GJ, Hinds MG, Francalanci F, Wilson R, Broemer M, Santoro MM, Day CL, Meier P Mol Cell. 2011 Jun 10;42(5):569-83. Epub 2011 May 5. PMID:21549626<ref>PMID:21549626</ref> | CARD-mediated autoinhibition of cIAP1's E3 ligase activity suppresses cell proliferation and migration.,Lopez J, John SW, Tenev T, Rautureau GJ, Hinds MG, Francalanci F, Wilson R, Broemer M, Santoro MM, Day CL, Meier P Mol Cell. 2011 Jun 10;42(5):569-83. Epub 2011 May 5. PMID:21549626<ref>PMID:21549626</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 2l9m" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Day CL]] |
| - | [[Category: | + | [[Category: Hinds MG]] |
| - | [[Category: | + | [[Category: Rautureau GJP]] |
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Current revision
Structure of cIAP1 CARD
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