Source:http://linkedlifedata.com/resource/pubmed/id/12488316
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2003-3-17
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pubmed:abstractText |
Degradation of cytosolic proteins depends largely on the proteasome, and a fraction of the cleavage products are presented as major histocompatibility complex (MHC) class I-bound ligands at the cell surface of antigen presenting cells. Proteolytic pathways accessory to the proteasome contribute to protein turnover, and their up-regulation may complement the proteasome when proteasomal proteolysis is impaired. Here we show that reduced reliance on proteasomal proteolysis allowed a reduced efficiency of MHC class I ligand production, whereas protein turnover and cellular proliferation were maintained. Using the proteasomal inhibitor adamantane-acetyl-(6-aminohexanoyl)3-(leucinyl)3-vinyl-(methyl)-sulphone, we show that covalent inhibition of all three types of proteasomal beta-subunits (beta(1), beta(2), and beta(5)) was compatible with continued growth in cells that up-regulate accessory proteolytic pathways, which include cytosolic proteases as well as deubiquitinating enzymes. However, under these conditions, we observed poor assembly of H-2D(b) molecules and inhibited presentation of endogenous tumor antigens. Thus, the tight link between protein turnover and production of MHC class I ligands can be broken by enforcing the substitution of the proteasome with alternative proteolytic pathways.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxy-5-iodo-3-nitrophenylacetyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/H-2Kb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10013-21
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12488316-Animals,
pubmed-meshheading:12488316-Antigen Presentation,
pubmed-meshheading:12488316-Cysteine Endopeptidases,
pubmed-meshheading:12488316-Cytosol,
pubmed-meshheading:12488316-H-2 Antigens,
pubmed-meshheading:12488316-Histocompatibility Antigens Class I,
pubmed-meshheading:12488316-Mice,
pubmed-meshheading:12488316-Mice, Inbred C57BL,
pubmed-meshheading:12488316-Multienzyme Complexes,
pubmed-meshheading:12488316-Oligopeptides,
pubmed-meshheading:12488316-Proteasome Endopeptidase Complex,
pubmed-meshheading:12488316-Sulfones,
pubmed-meshheading:12488316-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:12488316-Ubiquitin
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pubmed:year |
2003
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pubmed:articleTitle |
Pathways accessory to proteasomal proteolysis are less efficient in major histocompatibility complex class I antigen production.
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pubmed:affiliation |
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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