| http://purl.uniprot.org/citations/15888658 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15888658 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15888658 | http://www.w3.org/2000/01/rdf-schema#comment | "Regulation of the process of neuronal death plays a central role both during development of the CNS and in adult brain. The transcription factor myocyte enhancer factor 2 (MEF2) plays a critical role in neuronal survival. Cyclin-dependent kinase 5 (Cdk5) mediates neurotoxic effects by phosphorylating and inhibiting MEF2. How Cdk5-dependent phosphorylation reduces MEF2 transactivation activity remained unknown. Here, we demonstrate a novel mechanism by which Cdk5, in conjunction with caspase, inhibits MEF2. Using primary cerebellar granule neuron as a model, our investigation reveals that neurotoxicity induces destabilization of MEF2s in neurons. Destabilization of MEF2 is caused by an increase in caspase-dependent cleavage of MEF2. This cleavage event requires nuclear activation of Cdk5 activity. Phosphorylation by Cdk5 alone is sufficient to promote degradation of MEF2A and MEF2D by caspase-3. In contrast to MEF2A and MEF2D, MEF2C is not phosphorylated by Cdk5 after glutamate exposure and, therefore, resistant to neurotoxin-induced caspase-dependent degradation. Consistently, blocking Cdk5 or enhancing MEF2 reduced toxin-induced apoptosis. These findings define an important regulatory mechanism that for the first time links prodeath activities of Cdk5 and caspase. The convergence of Cdk5 phosphorylation-dependent caspase-mediated degradation of nuclear survival factors exemplified by MEF2 may represent a general process applicable to the regulation of other survival factors under diverse neurotoxic conditions."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.1331-05.2005"xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.org/dc/terms/identifier | "doi:10.1523/jneurosci.1331-05.2005"xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Gong X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Gong X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Park D."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Park D."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Tang X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Tang X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Wang X."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Xia Z."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Xia Z."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Mao Z."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Mao Z."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Tong M."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/author | "Tong M."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/name | "J. Neurosci."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/name | "J. Neurosci."xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/pages | "4823-4834"xsd:string |
| http://purl.uniprot.org/citations/15888658 | http://purl.uniprot.org/core/pages | "4823-4834"xsd:string |