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rdf:type |
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lifeskim:mentions |
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0026882,
umls-concept:C0038838,
umls-concept:C0205360,
umls-concept:C0208973,
umls-concept:C1514526,
umls-concept:C1517892,
umls-concept:C1704666,
umls-concept:C1862939,
umls-concept:C2349975
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pubmed:issue |
1
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pubmed:dateCreated |
1996-12-23
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pubmed:abstractText |
Point mutations occurring within the Cu/Zn superoxide dismutase (SOD1) gene have been implicated in the etiology of some cases of familial amyotrophic lateral sclerosis (FALS). In order to better understand the functional consequences of these mutations, we have introduced FALS mutations into the mouse SOD1 gene and studied the expression of the mutant templates in stably transformed cell lines. Pulse-chase analyses of lysates derived from cell lines stably expressing the Cu/Zn SOD isoforms indicate that the FALS mutant Cu/Zn SOD proteins are turned over more rapidly than wild-type SOD. Protease inhibitors specific for the major intracellular proteolytic activities were used to characterize the degradative pathways involved in the turnover of mutant Cu/Zn SOD. Inhibition of the chymotrypsin-like activity of the proteasome (also known as multicatalytic proteinase or ubiquitin, ATP-dependent proteinase) by a synthetic dipeptide aldehyde led to a significant increase in levels of the mutant Cu/Zn SOD implicating this proteolytic pathway in the turnover of the FALS mutant SOD proteins.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0022-510X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
139
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15-20
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8836967-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:8836967-Animals,
pubmed-meshheading:8836967-Base Sequence,
pubmed-meshheading:8836967-Cell Line,
pubmed-meshheading:8836967-Consensus Sequence,
pubmed-meshheading:8836967-Cysteine Endopeptidases,
pubmed-meshheading:8836967-Humans,
pubmed-meshheading:8836967-Isoenzymes,
pubmed-meshheading:8836967-Kidney,
pubmed-meshheading:8836967-Kinetics,
pubmed-meshheading:8836967-Mice,
pubmed-meshheading:8836967-Multienzyme Complexes,
pubmed-meshheading:8836967-Point Mutation,
pubmed-meshheading:8836967-Protease Inhibitors,
pubmed-meshheading:8836967-Proteasome Endopeptidase Complex,
pubmed-meshheading:8836967-Recombinant Proteins,
pubmed-meshheading:8836967-Superoxide Dismutase,
pubmed-meshheading:8836967-Transfection
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pubmed:year |
1996
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pubmed:articleTitle |
Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis.
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pubmed:affiliation |
Department of Molecular Biology, Cephalon, Inc., West Chester, PA 19380, USA.
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pubmed:publicationType |
Journal Article
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