| http://purl.uniprot.org/citations/25296760 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25296760 | http://www.w3.org/2000/01/rdf-schema#comment | "Post-translational modification by ubiquitin plays important roles in multiple physiological and pathological processes. Ubiquitin-binding proteins play a critical role in recognizing and relaying polyubiquitin-based signaling. NEMO (NF-κB Essential Modulator) is a central player in canonical NF-κB signaling whose major function is to bind to Lys-63- and/or M1-(or linear) linked polyubiquitin chains generated in response to cell stimulation. Here we show that Withaferin A (WA), a steroidal lactone, causes a change in NEMO's interaction with specific types of polyubiquitin chains in vitro. WA induces full-length recombinant NEMO to bind to long Lys-48-linked polyubiquitin chains but not tetra-ubiquitin species. Significantly, the UBAN (ubiquitin binding in ABIN and NEMO) domain, essential for the ability of NEMO to bind M1/Lys-63-linked polyubiquitin, is dispensable for the WA-induced gain-of-function activity. Mass spectrometric analysis demonstrated that WA covalently modifies NEMO on a cysteine residue within the C-terminal zinc finger (ZF) domain. Point mutations to the ZF can reverse the WA-induced Lys-48-polyubiquitin binding phenotype. Our study demonstrates the feasibility of directly altering the ubiquitin interaction properties of an ubiquitin-binding protein by a chemical compound, thereby shedding light on a novel drug class to potentially alter polyubiquitin-based cellular processes."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m114.582478"xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/author | "Miyamoto S."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/author | "Coon J.J."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/author | "Jackson S.S."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/author | "Hooper C."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/author | "Coughlin E.E."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/pages | "33161-33174"xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/title | "Covalent modification of the NF-kappaB essential modulator (NEMO) by a chemical compound can regulate its ubiquitin binding properties in vitro."xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://purl.uniprot.org/core/volume | "289"xsd:string |
| http://purl.uniprot.org/citations/25296760 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25296760 |
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