Linked Life Data

12401807

Source:http://linkedlifedata.com/resource/pubmed/id/12401807

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-12-30
pubmed:abstractText
Oxidatively modified proteins that accumulate in aging and many diseases can form large aggregates because of covalent cross-linking or increased surface hydrophobicity. Unless repaired or removed from cells, these oxidized proteins are often toxic, and threaten cell viability. Most oxidatively damaged proteins appear to undergo selective proteolysis, primarily by the proteasome. Previous work from our laboratory has shown that purified 20 S proteasome degrades oxidized proteins without ATP or ubiquitin in vitro, but there have been no studies to test this mechanism in vivo. The aim of this study was to determine whether ubiquitin conjugation is necessary for the degradation of oxidized proteins in intact cells. We now show that cells with compromised ubiquitin-conjugating activity still preferentially degrade oxidized intracellular proteins, at near normal rates, and this degradation is still inhibited by proteasome inhibitors. We also show that progressive oxidation of proteins such as lysozyme and ferritin does not increase their ubiquitinylation, yet the oxidized forms of both proteins are preferentially degraded by proteasome. Furthermore, rates of oxidized protein degradation by cell lysates are not significantly altered by addition of ATP, excluding the possibility of an energy requirement for this pathway. Contrary to earlier popular belief that most proteasomal degradation is conducted by the 26 S proteasome with ubiquitinylated substrates, our work suggests that oxidized proteins are degraded without ubiquitin conjugation (or ATP hydrolysis) possibly by the 20 S proteasome, or the immunoproteasome, or both.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
311-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12401807-Adenosine Triphosphate, pubmed-meshheading:12401807-Animals, pubmed-meshheading:12401807-Cell Cycle, pubmed-meshheading:12401807-Cell Line, pubmed-meshheading:12401807-Cell Survival, pubmed-meshheading:12401807-Cricetinae, pubmed-meshheading:12401807-Cysteine Endopeptidases, pubmed-meshheading:12401807-Ferritins, pubmed-meshheading:12401807-Fibroblasts, pubmed-meshheading:12401807-Hot Temperature, pubmed-meshheading:12401807-Hydrogen Peroxide, pubmed-meshheading:12401807-Lung, pubmed-meshheading:12401807-Multienzyme Complexes, pubmed-meshheading:12401807-Muramidase, pubmed-meshheading:12401807-Oxidation-Reduction, pubmed-meshheading:12401807-Oxidative Stress, pubmed-meshheading:12401807-Proteasome Endopeptidase Complex, pubmed-meshheading:12401807-Protein Denaturation, pubmed-meshheading:12401807-Ubiquitin
pubmed:year
2003
pubmed:articleTitle
Ubiquitin conjugation is not required for the degradation of oxidized proteins by proteasome.
pubmed:affiliation
Ethel Percy Andrus Gerontology Center and Division of Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089-0191, USA. Reshma_Shringarpure@dfci.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.