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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2007-2-7
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pubmed:abstractText |
L-arginine (L-Arg) plays a central role in several biologic systems including the regulation of T-cell function. L-Arg depletion by myeloid-derived suppressor cells producing arginase I is seen in patients with cancer inducing T-cell anergy. We studied how L-Arg starvation could regulate T-cell-cycle progression. Stimulated T cells cultured in the absence of L-Arg are arrested in the G0-G1phase of the cell cycle. This was associated with an inability of T cells to up-regulate cyclin D3 and cyclin-dependent kinase 4 (cdk4), but not cdk6, resulting in an impaired downstream signaling with a decreased phosphorylation of Rb protein and a low expression and binding of E2F1. Silencing of cyclin D3 reproduced the cell cycle arrest caused by L-Arg starvation. The regulation of cyclin D3 and cdk4 by L-Arg starvation occurs at transcriptional and posttranscriptional levels. Signaling through GCN2 kinase is triggered during amino acid starvation. Experiments demonstrated that T cells from GCN2 knock-out mice did not show a decreased proliferation and were able to up-regulate cyclin D3 when cultured in the absence of L-Arg. These results contribute to the understanding of a central mechanism by which cancer and other diseases characterized by high arginase I production may cause T-cell dysfunction.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-10508164,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-10521420,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-10893433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-10998343,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-11311938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-11942557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-11950832,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-12459251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-12655043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-12874210,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15028568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15210820,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15313928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15465778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15465781,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15544543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15833831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15894280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-15922712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-16056256,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-2135757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-5038266,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-8140629,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-8617286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-8939918,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-9242663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17023580-9932681
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/CCND3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D3,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Eif2ak4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1568-73
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17023580-Animals,
pubmed-meshheading:17023580-Arginine,
pubmed-meshheading:17023580-Cell Cycle,
pubmed-meshheading:17023580-Cell Proliferation,
pubmed-meshheading:17023580-Clonal Anergy,
pubmed-meshheading:17023580-Cyclin D3,
pubmed-meshheading:17023580-Cyclin-Dependent Kinases,
pubmed-meshheading:17023580-Cyclins,
pubmed-meshheading:17023580-Gene Expression Regulation,
pubmed-meshheading:17023580-Humans,
pubmed-meshheading:17023580-Mice,
pubmed-meshheading:17023580-Mice, Knockout,
pubmed-meshheading:17023580-Neoplasms,
pubmed-meshheading:17023580-Protein-Serine-Threonine Kinases,
pubmed-meshheading:17023580-T-Lymphocytes
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pubmed:year |
2007
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pubmed:articleTitle |
L-arginine availability regulates T-lymphocyte cell-cycle progression.
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pubmed:affiliation |
Tumor Immunology Program, Stanley S. Scott Cancer Center, Lousiana State University Health Sciences Center, Department of Pediatrics, New Orleans 70112, USA. prodri1@lsuhsc.edu
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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