Source:http://linkedlifedata.com/resource/pubmed/id/12594855
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2003-2-20
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| pubmed:abstractText |
Tapasin is a member of the MHC class I loading complex where it bridges the TAP peptide transporter to class I molecules. The main role of tapasin is assumed to be the facilitation of peptide loading and optimization of the peptide cargo. Here, we describe another important function for tapasin. In tapasin-deficient (Tpn(-/-)) mice the absence of tapasin was found to have a dramatic effect on the stability of the TAP1/TAP2 heterodimeric peptide transporter. Steady-state expression of TAP protein was reduced more than 100-fold from about 3 x 10(4) TAP molecules per wild-type splenocyte to about 1 x 10(2) TAP per Tpn(-/-) splenocyte. Thus, a major function of murine tapasin appears to be the stabilization of TAP. The low amount of TAP moleculesin Tpn(-/-) lymphocytes is likely to contribute to the severe impairment of MHC class I expression. Surprisingly, activation of Tpn(-/-) lymphocytes yielded strongly enhanced class I expression comparable to wild-type levels, although TAP expression remained low and in the magnitude of several hundred molecules per cell. The high level of class I on activated Tpn(-/-) cells depended on peptides generated by the proteasome as indicated by blockade with the proteasome-specific inhibitor lactacystin. Lymphocyte activation induced an increase in ubiquitinated proteins that are cleaved into peptides by the proteasome. These findings suggest that in the presence of a large peptide pool in the cytosol, a small number of TAP transporters is sufficient to translocate enough peptides for high class I expression. However, these class I molecules were less stable than those of wild-type cells, indicating that tapasin is not only required for stabilization of TAP but also for optimization of the spectrum of bound peptides.
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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/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Antiporters,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/TAP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TAP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tap1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tap2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/tapasin
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0014-2980
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
33
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
264-73
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:12594855-ATP-Binding Cassette Transporters,
pubmed-meshheading:12594855-Animals,
pubmed-meshheading:12594855-Antiporters,
pubmed-meshheading:12594855-Biological Transport,
pubmed-meshheading:12594855-Cell Death,
pubmed-meshheading:12594855-Cell Line,
pubmed-meshheading:12594855-Cysteine Endopeptidases,
pubmed-meshheading:12594855-Gene Deletion,
pubmed-meshheading:12594855-Gene Expression Regulation,
pubmed-meshheading:12594855-Half-Life,
pubmed-meshheading:12594855-Histocompatibility Antigens Class I,
pubmed-meshheading:12594855-Humans,
pubmed-meshheading:12594855-Immunoglobulins,
pubmed-meshheading:12594855-Lymphocyte Activation,
pubmed-meshheading:12594855-Membrane Transport Proteins,
pubmed-meshheading:12594855-Mice,
pubmed-meshheading:12594855-Mice, Knockout,
pubmed-meshheading:12594855-Multienzyme Complexes,
pubmed-meshheading:12594855-Proteasome Endopeptidase Complex,
pubmed-meshheading:12594855-Ubiquitin
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| pubmed:year |
2003
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| pubmed:articleTitle |
A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression.
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| pubmed:affiliation |
Deutsches Krebsforschungszentrum Heidelberg, Abteilung Molekulare Immunologie, Heidelberg, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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