Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death

F M De Vrij; J A Sluijs; L Gregori; D F Fischer; W T Hermens; D Goldgaber; J Verhaagen; F W Van Leeuwen; E M Hol

doi:10.1096/fj.01-0438com

Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death

F M De Vrij, J A Sluijs, L Gregori, D F Fischer, W T Hermens, D Goldgaber, J Verhaagen, F W Van Leeuwen, E M Hol

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	2680-8
Number of pages	9
Journal	FASEB Journal
Volume	15
Issue number	14
DOIs	https://doi.org/10.1096/fj.01-0438com
Publication status	Published - Dec 2001

Keywords

Adenosine Triphosphate
Adenoviridae
Alzheimer Disease
Apoptosis
Blotting, Western
Cell Nucleus
Cysteine Endopeptidases
Genetic Vectors
Humans
Lac Operon
Multienzyme Complexes
Mutation
Neurons
Proteasome Endopeptidase Complex
Proteins
Recombinant Fusion Proteins
Signal Transduction
Tumor Cells, Cultured
Ubiquitin
Journal Article
Research Support, Non-U.S. Gov't

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10.1096/fj.01-0438com

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@article{26407157e1b64ca1a400988717f05273,

title = "Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death",

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.",

keywords = "Adenosine Triphosphate, Adenoviridae, Alzheimer Disease, Apoptosis, Blotting, Western, Cell Nucleus, Cysteine Endopeptidases, Genetic Vectors, Humans, Lac Operon, Multienzyme Complexes, Mutation, Neurons, Proteasome Endopeptidase Complex, Proteins, Recombinant Fusion Proteins, Signal Transduction, Tumor Cells, Cultured, Ubiquitin, Journal Article, Research Support, Non-U.S. Gov't",

author = "{De Vrij}, {F M} and Sluijs, {J A} and L Gregori and Fischer, {D F} and Hermens, {W T} and D Goldgaber and J Verhaagen and {Van Leeuwen}, {F W} and Hol, {E M}",

year = "2001",

month = dec,

doi = "10.1096/fj.01-0438com",

language = "English",

volume = "15",

pages = "2680--8",

journal = "FASEB Journal",

issn = "0892-6638",

publisher = "John Wiley & Sons Inc.",

number = "14",

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TY - JOUR

T1 - Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death

AU - De Vrij, F M

AU - Sluijs, J A

AU - Gregori, L

AU - Fischer, D F

AU - Hermens, W T

AU - Goldgaber, D

AU - Verhaagen, J

AU - Van Leeuwen, F W

AU - Hol, E M

PY - 2001/12

Y1 - 2001/12

N2 - 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.

AB - 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.

KW - Adenosine Triphosphate

KW - Adenoviridae

KW - Alzheimer Disease

KW - Apoptosis

KW - Blotting, Western

KW - Cell Nucleus

KW - Cysteine Endopeptidases

KW - Genetic Vectors

KW - Humans

KW - Lac Operon

KW - Multienzyme Complexes

KW - Mutation

KW - Neurons

KW - Proteasome Endopeptidase Complex

KW - Proteins

KW - Recombinant Fusion Proteins

KW - Signal Transduction

KW - Tumor Cells, Cultured

KW - Ubiquitin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1096/fj.01-0438com

DO - 10.1096/fj.01-0438com

M3 - Article

C2 - 11726544

SN - 0892-6638

VL - 15

SP - 2680

EP - 2688

JO - FASEB Journal

JF - FASEB Journal

IS - 14

ER -

Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death

Abstract

Keywords

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