| http://purl.uniprot.org/citations/22419809 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22419809 | http://www.w3.org/2000/01/rdf-schema#comment | "The adenovirus early region 1A (E1A) protein promotes cell immortalization and transformation by mediating the activities of key cellular regulators. The repressor element 1-silencing transcription factor (REST), which is a major neuronal and tumor suppressor, was previously found mainly in the cytoplasm rather than in the nuclei of adenovirus-transformed rodent cells (22). We now demonstrate that the loss of REST in the nucleus is due to its rapid degradation by the ubiquitin-proteasome system. Only nuclear REST, but not its cytoplasmic counterpart, was ubiquitinated and degraded. REST degradation was blocked by the ubiquitination inhibitor PYR-41 and the proteasome inhibitor MG-132 but not by the nuclear export inhibitor leptomycin B. REST degradation required both of its two C-terminal degrons that are recognized by the ubiquitin ligase SCF(β-TrCP), since deletion or mutation of either degron eliminated degradation. Importantly, E1A was shown to mediate REST ubiquitination and degradation by upregulating β-TrCP. Knockdown of E1A in virus-transformed cells reduced both β-TrCP and ubiquitination of nuclear REST. In contrast, when expressed in HeLa cells, E1A enhanced the degradation of nuclear REST. Reconstitution of REST in virus-transformed cells negatively affected E1A-mediated cell proliferation and anchorage-independent growth. These data strongly indicate that E1A stimulates ubiquitination and proteolysis of REST in the nucleus, thereby abolishing the tumor suppressor functions of REST."xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.org/dc/terms/identifier | "doi:10.1128/jvi.06811-11"xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/author | "Guan H."xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/author | "Ricciardi R.P."xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/name | "J Virol"xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/pages | "5594-5602"xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/title | "Transformation by E1A oncoprotein involves ubiquitin-mediated proteolysis of the neuronal and tumor repressor REST in the nucleus."xsd:string |
| http://purl.uniprot.org/citations/22419809 | http://purl.uniprot.org/core/volume | "86"xsd:string |
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