| http://purl.uniprot.org/citations/19224863 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19224863 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19224863 | http://www.w3.org/2000/01/rdf-schema#comment | "Parkinson disease (PD) is characterized by the presence of ubiquitylated inclusions and the death of dopaminergic neurons. Seven in absentia homolog (SIAH) is a ubiquitin-ligase that ubiquitylates alpha-synuclein and synphilin-1 and is present in Lewy bodies of PD patients. Understanding the mechanisms that regulate the ubiquitylation of PD-related proteins might shed light on the events involved in the formation of Lewy bodies and death of neurons. We show in this study that the recently described synphilin-1 isoform, synphilin-1A, interacts in vitro and in vivo with the ubiquitin-protein isopeptide ligase SIAH and regulates its activity toward alpha-synuclein and synphilin-1. SIAH promotes limited ubiquitylation of synphilin-1A that does not lead to its degradation by the proteasome. SIAH also increases the formation of synphilin-1A inclusions in the presence of proteasome inhibitors, supporting the participation of ubiquitylated synphilin-1A in the formation of Lewy body-like inclusions. Synphilin-1A/SIAH inclusions recruit PD-related proteins, such as alpha-synuclein, synphilin-1, Parkin, PINK1, and UCH-L1. We found that synphilin-1A robustly increases the steady-state levels of SIAH by decreasing its auto-ubiquitylation and degradation. In addition, synphilin-1A blocks the ubiquitylation and degradation of the SIAH substrates synphilin-1 and deleted in colon cancer protein. Furthermore, synphilin-1A strongly decreases the monoubiquitylation of alpha-synuclein by SIAH and the formation of alpha-synuclein inclusions, supporting a role for monoubiquitylation in alpha-synuclein inclusion formation. Our results suggest a novel function for synphilin-1A as a regulator of SIAH activity and formation of Lewy body-like inclusions."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m805990200"xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m805990200"xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Rott R."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Rott R."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Wolosker H."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Wolosker H."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Engelender S."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Engelender S."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Szargel R."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Szargel R."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Balan L."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Balan L."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Eyal A."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Eyal A."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Haskin J."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Haskin J."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Shani V."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/author | "Shani V."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/19224863 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |