Abstract
Ubiquitin-B+1 (UBB+1) is a mutant ubiquitin that accumulates in the neurones of patients with Alzheimer's disease (AD). Here we report on the biochemical and functional differences between ubiquitin and UBB+1 and the effect of the mutant protein on neuronal cells. UBB+1 lacks the capacity to ubiquitinate, and although it is ubiquitinated itself, UBB+1 is not degraded by the ubiquitin-proteasomal system and is quite stable in neuronal cells. Overexpression of UBB+1 in neuroblastoma cells significantly induces nuclear fragmentation and cell death. Our results demonstrate that accumulation of UBB+1 in neurones is detrimental and may contribute to neuronal dysfunction in AD patients.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / pharmacology
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Adenoviridae / genetics
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Alzheimer Disease / genetics
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Alzheimer Disease / pathology*
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Apoptosis / physiology*
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Blotting, Western
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Cell Nucleus / metabolism
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Cysteine Endopeptidases / drug effects
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Cysteine Endopeptidases / metabolism
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Genetic Vectors / genetics
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Humans
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Lac Operon / genetics
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Multienzyme Complexes / drug effects
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Multienzyme Complexes / metabolism
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Mutation
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Neurons / cytology*
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Neurons / metabolism
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Proteasome Endopeptidase Complex
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Proteins / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / drug effects
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Tumor Cells, Cultured
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Ubiquitin / drug effects
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Ubiquitin / genetics*
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Ubiquitin / metabolism
Substances
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Multienzyme Complexes
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Proteins
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Recombinant Fusion Proteins
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Ubiquitin
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Adenosine Triphosphate
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex