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http://purl.uniprot.org/citations/18354482http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18354482http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18354482http://www.w3.org/2000/01/rdf-schema#comment"REST/NRSF (repressor-element-1-silencing transcription factor/neuron-restrictive silencing factor) negatively regulates the transcription of genes containing RE1 sites. REST is expressed in non-neuronal cells and stem/progenitor neuronal cells, in which it inhibits the expression of neuron-specific genes. Overexpression of REST is frequently found in human medulloblastomas and neuroblastomas, in which it is thought to maintain the stem character of tumour cells. Neural stem cells forced to express REST and c-Myc fail to differentiate and give rise to tumours in the mouse cerebellum. Expression of a splice variant of REST that lacks the carboxy terminus has been associated with neuronal tumours and small-cell lung carcinomas, and a frameshift mutant (REST-FS), which is also truncated at the C terminus, has oncogenic properties. Here we show, by using an unbiased screen, that REST is an interactor of the F-box protein beta-TrCP. REST is degraded by means of the ubiquitin ligase SCF(beta-TrCP) during the G2 phase of the cell cycle to allow transcriptional derepression of Mad2, an essential component of the spindle assembly checkpoint. The expression in cultured cells of a stable REST mutant, which is unable to bind beta-TrCP, inhibited Mad2 expression and resulted in a phenotype analogous to that observed in Mad2(+/-) cells. In particular, we observed defects that were consistent with faulty activation of the spindle checkpoint, such as shortened mitosis, premature sister-chromatid separation, chromosome bridges and mis-segregation in anaphase, tetraploidy, and faster mitotic slippage in the presence of a spindle inhibitor. An indistinguishable phenotype was observed by expressing the oncogenic REST-FS mutant, which does not bind beta-TrCP. Thus, SCF(beta-TrCP)-dependent degradation of REST during G2 permits the optimal activation of the spindle checkpoint, and consequently it is required for the fidelity of mitosis. The high levels of REST or its truncated variants found in certain human tumours may contribute to cellular transformation by promoting genomic instability."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.org/dc/terms/identifier"doi:10.1038/nature06641"xsd:string
http://purl.uniprot.org/citations/18354482http://purl.org/dc/terms/identifier"doi:10.1038/nature06641"xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Chang S."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Chang S."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Cardozo T."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Cardozo T."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Pagano M."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Pagano M."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Peschiaroli A."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Peschiaroli A."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Guardavaccaro D."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Guardavaccaro D."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Frescas D."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Frescas D."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Hernando E."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Hernando E."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Dorrello N.V."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Dorrello N.V."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Iavarone A."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Iavarone A."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Lasorella A."xsd:string
http://purl.uniprot.org/citations/18354482http://purl.uniprot.org/core/author"Lasorella A."xsd:string
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