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Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death 1
Author(s) -
De Vrij Femke M. S.,
Sluijs Jacqueline A.,
Gregori Luisa,
Fischer David F.,
Hermens Wim T. J. M. C.,
Goldgaber Dmitry,
Verhaagen Joost,
Van Leeuwen Fred W.,
Hol Elly M.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0438com
Subject(s) - ubiquitin , mutant , programmed cell death , microbiology and biotechnology , fragmentation (computing) , chemistry , deubiquitinating enzyme , ubiquitin ligase , biology , apoptosis , biochemistry , gene , ecology
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 ubiquiti‐nate, 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.—de Vrij, F. M. S., Sluijs, J. A., Gregori, L., Fischer, D. F., Hermens, W. T. J. M. C., Goldgaber, D., Verhaagen, J., van Leeuwen, F. W., Hol, E. M. Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death. FASEB J. 15, 2680–2688 (2001)