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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2001-9-6
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pubmed:abstractText |
The inhibitors of cyclin-dependent kinase (CDK) 4 (INK4) bind CDK4/6 to prevent their association with D-cyclins and G(1) cell cycle initiation and progression. We report here that among the seven CDK inhibitors, p18(INK4c) played an important role in modulating TCR-mediated T cell proliferation. Loss of p18(INK4c) in T cells led to hyperproliferation in response to CD3 stimulation. p18(INK4c)-null mice developed lymphoproliferative disorder and T cell lymphomas. Expression of IL-2, IL-2R-alpha, and the major G(1) cell cycle regulatory proteins was not altered in p18-null T cells. Both FK506 and rapamycin efficiently inhibited proliferation of p18-null T cells. In activated T cells, p18(INK4c) remained constant, and preferentially associated with and inhibited CDK6 but not CDK4. We propose that p18(INK4c) sets an inhibitory threshold in T cells and one function of CD28 costimulation is to counteract the p18(INK4c) inhibitory activity on CDK6-cyclin D complexes. The p18(INK4c) protein may provide a novel target to modulate T cell immunity.
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pubmed:grant |
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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/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn2c protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Sirolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Tacrolimus,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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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 |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3285-92
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11544316-Animals,
pubmed-meshheading:11544316-Antigens, CD28,
pubmed-meshheading:11544316-Antigens, CD3,
pubmed-meshheading:11544316-CDC2-CDC28 Kinases,
pubmed-meshheading:11544316-Cell Cycle,
pubmed-meshheading:11544316-Cell Cycle Proteins,
pubmed-meshheading:11544316-Cell Division,
pubmed-meshheading:11544316-Cyclin-Dependent Kinase 2,
pubmed-meshheading:11544316-Cyclin-Dependent Kinase 4,
pubmed-meshheading:11544316-Cyclin-Dependent Kinase 6,
pubmed-meshheading:11544316-Cyclin-Dependent Kinase Inhibitor p18,
pubmed-meshheading:11544316-Cyclin-Dependent Kinases,
pubmed-meshheading:11544316-Cytokines,
pubmed-meshheading:11544316-Enzyme Inhibitors,
pubmed-meshheading:11544316-G1 Phase,
pubmed-meshheading:11544316-Immunosuppressive Agents,
pubmed-meshheading:11544316-Lymphocyte Activation,
pubmed-meshheading:11544316-Lymphoma, T-Cell,
pubmed-meshheading:11544316-Lymphoproliferative Disorders,
pubmed-meshheading:11544316-Mice,
pubmed-meshheading:11544316-Mice, Knockout,
pubmed-meshheading:11544316-Mice, SCID,
pubmed-meshheading:11544316-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11544316-Proto-Oncogene Proteins,
pubmed-meshheading:11544316-Receptors, Antigen, T-Cell,
pubmed-meshheading:11544316-Sirolimus,
pubmed-meshheading:11544316-T-Lymphocyte Subsets,
pubmed-meshheading:11544316-Tacrolimus,
pubmed-meshheading:11544316-Tumor Suppressor Proteins
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pubmed:year |
2001
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pubmed:articleTitle |
An important role of CDK inhibitor p18(INK4c) in modulating antigen receptor-mediated T cell proliferation.
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pubmed:affiliation |
Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill, NC 27599, 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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