Document Detail

Polyglutamine-mediated aggregation and cell death.
MedLine Citation:
PMID:  10860836     Owner:  NLM     Status:  MEDLINE    
The expansion of CAG repeats is the genetic defect underlying eight neurodegenerative diseases. A common feature of these disorders is the presence of intracellular aggregates in neuronal cells. It is still unclear the significance of these cellular inclusions in the neurodegenerative process, since cell death without aggregate formation has been reported. We have constructed a synthetic fusion protein containing 17 or 43 CAG repeats and the green fluorescent protein that recapitulates the features of CAG-expanded alleles. Expression of 43, but not 17 CAG repeats results in formation of nuclear aggregates in human neuroblastoma cells. Moreover, the normal allele (17 CAG) is sequestered in the inclusion bodies. The presence of nuclear inclusions tightly correlates with apoptosis in cells expressing the protein encoding 43 CAG repeats. Cells harboring nuclear aggregates stop proliferation and undergo apoptosis. Moreover, the inhibition of protein degradation pathway increases intracellular aggregates and cell death. These data indicate that intranuclear aggregates induce apoptosis and suggest that the degradation of unfolded proteins improves cell survival.
T de Cristofaro; A Affaitati; A Feliciello; E V Avvedimento; S Varrone
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  272     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2000 Jun 
Date Detail:
Created Date:  2000-07-26     Completed Date:  2000-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  816-21     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli "Federico II", Via Pansini 5, Naples, Italy.
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MeSH Terms
Cell Division
Cell Nucleus / metabolism,  pathology
Cell Survival
Cysteine Endopeptidases / metabolism
Cytoplasm / metabolism,  pathology
Inclusion Bodies / metabolism,  pathology*
Microscopy, Fluorescence
Multienzyme Complexes / metabolism
Neuroblastoma / metabolism,  pathology*
Peptides / chemistry,  genetics,  metabolism*
Proteasome Endopeptidase Complex
Protein Binding
Recombinant Fusion Proteins / chemistry,  genetics,  metabolism
Repetitive Sequences, Amino Acid / genetics,  physiology*
Time Factors
Trinucleotide Repeat Expansion / genetics
Tumor Cells, Cultured
Reg. No./Substance:
0/Multienzyme Complexes; 0/Peptides; 0/Recombinant Fusion Proteins; 26700-71-0/polyglutamine; EC 3.4.22.-/Cysteine Endopeptidases; EC Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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