RGD Reference Report - Proteasomal inhibition-induced inclusion formation and death in cortical neurons require transcription and ubiquitination. - Rat Genome Database

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Proteasomal inhibition-induced inclusion formation and death in cortical neurons require transcription and ubiquitination.

Authors: Rideout, HJ  Stefanis, L 
Citation: Rideout HJ and Stefanis L, Mol Cell Neurosci. 2002 Oct;21(2):223-38.
RGD ID: 2316159
Pubmed: PMID:12401444   (View Abstract at PubMed)

Increasing evidence suggests that proteasomal dysfunction plays a role in the pathogenesis of Lewy body diseases. We have used pharmacological inhibitors of the proteasome to model proteasomal dysfunction in cultured rat cortical neurons. Proteasomal inhibition induced apoptotic death and formation of cytoplasmic ubiquitinated inclusions, which were present only in viable neurons. Actinomycin D, but not a caspase inhibitor, prevented inclusion formation, whereas both agents inhibited cell death. alpha-Synuclein and thioflavin S staining were found within the inclusions. alpha-Synuclein, however, did not appear to be ubiquitinated or aggregated. A dominant-negative mutant of an E2 ubiquitin-conjugating enzyme, cdc34, prevented inclusion formation and attenuated cell death. Our results suggest that in cortical neurons: (a) proteasomal dysfunction plays a role in formation of ubiquitin/alpha-synuclein-positive inclusions, (b) inclusion formation is an active cell process requiring transcription, and (c) ubiquitination of certain proteins is required for inclusion formation and may participate in neuronal death.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of inclusion body assembly  IMP 2316159 RGD 
positive regulation of neuron apoptotic process  IMP 2316159 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdc34  (cell division cycle 34, ubiqiutin conjugating enzyme)


Additional Information