RGD Reference Report - Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity. - Rat Genome Database

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Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity.

Authors: Kravchick, Dana O  Karpova, Anna  Hrdinka, Matous  Lopez-Rojas, Jeffrey  Iacobas, Sanda  Carbonell, Abigail U  Iacobas, Dumitru A  Kreutz, Michael R  Jordan, Bryen A 
Citation: Kravchick DO, etal., EMBO J. 2016 Sep 1;35(17):1923-34. doi: 10.15252/embj.201593070. Epub 2016 Jul 25.
RGD ID: 13702279
Pubmed: PMID:27458189   (View Abstract at PubMed)
PMCID: PMC5007554   (View Article at PubMed Central)
DOI: DOI:10.15252/embj.201593070   (Journal Full-text)

Elevated c-Jun levels result in apoptosis and are evident in neurodegenerative disorders such as Alzheimer's disease and dementia and after global cerebral insults including stroke and epilepsy. NMDA receptor (NMDAR) antagonists block c-Jun upregulation and prevent neuronal cell death following excitotoxic insults. However, the molecular mechanisms regulating c-Jun abundance in neurons are poorly understood. Here, we show that the synaptic component Proline rich 7 (PRR7) accumulates in the nucleus of hippocampal neurons following NMDAR activity. We find that PRR7 inhibits the ubiquitination of c-Jun by E3 ligase SCF(FBW) (7) (FBW7), increases c-Jun-dependent transcriptional activity, and promotes neuronal death. Microarray assays show that PRR7 abundance is directly correlated with transcripts associated with cellular viability. Moreover, PRR7 knockdown attenuates NMDAR-mediated excitotoxicity in neuronal cultures in a c-Jun-dependent manner. Our results show that PRR7 links NMDAR activity to c-Jun function and provide new insights into the molecular processes that underlie NMDAR-dependent excitotoxicity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glutamatergic synapse is_active_inIDA 13702279PMID:27458189SynGO 
glutamatergic synapse is_active_inIMP 13702279PMID:27458189SynGO 
neuron projection located_inIDA 13702279PMID:27458189UniProt 
nucleus located_inIDA 13702279PMID:27458189UniProt 
postsynaptic density located_inIDA 13702279PMID:27458189UniProt 
synapse located_inIDA 13702279PMID:27458189UniProt 

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Dlg4  (discs large MAGUK scaffold protein 4)
Grin1  (glutamate ionotropic receptor NMDA type subunit 1)
Prr7  (proline rich 7 (synaptic))


Additional Information