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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2003-9-30
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pubmed:abstractText |
Our studies address questions pertaining to the regulation of D cyclin-cdk4 activity, and the following results were obtained. Conditions that increased the abundance of the D cyclins also increased the abundance of enzymatically active D cyclin-cdk4 complexes in mouse embryo fibroblasts (MEFs) lacking both p27(Kip1) and p21(Cip1) (p27/p21(-/-)). Such conditions included ectopic expression of cyclin D1 and inhibition of D cyclin degradation by the proteasome inhibitor MG132. However, as determined by treatment of wild-type MEFs with MG132, maximal accumulation of D cyclin-cdk4 complexes required p27(Kip1) and p21(Cip1) and coincided with the formation of inactive D cyclin-cdk4-p27(Kip1) or -p21(Cip1) complexes. p27(Kip1) or p21(Cip1) also increased the abundance of D cyclin-cdk4 complexes and reduced amounts of cdk4 activity when ectopically expressed in p27/p21(-/-) MEFs. Lastly, increases in the stability of the D cyclins accounted for their greater abundance in wild-type MEFs than in p27/p21(-/-) MEFs. We conclude that (i) D cyclin-cdk4 complexes are formed and become active in the absence of p27(Kip1) and p21(Cip1) and (ii) p27(Kip1) and p21(Cip1) maximize the accumulation but inhibit the activity of D cyclin-cdk4 complexes. We suggest that D cyclin-cdk4 complexes are more stable when bound to p27(Kip1) or p21(Cip1) and that formation of ternary complexes also stabilizes the D cyclins.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-10075928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-10580009,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-10766840,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-11073976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-12034920,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-12444543,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-1423597,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-6246373,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-7831315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-7958854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-8114738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-8288131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-8339933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-8756624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-9106657,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-9136925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-9325318,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-9353308,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14517297-9832503
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Ccnd3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D3,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
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/Cyclins,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Leupeptins,
http://linkedlifedata.com/resource/pubmed/chemical/Multienzyme Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylleucyl-leucyl-leuci...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0270-7306
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7285-90
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14517297-Animals,
pubmed-meshheading:14517297-Blotting, Northern,
pubmed-meshheading:14517297-Blotting, Western,
pubmed-meshheading:14517297-Cell Cycle Proteins,
pubmed-meshheading:14517297-Cells, Cultured,
pubmed-meshheading:14517297-Cyclin D,
pubmed-meshheading:14517297-Cyclin D3,
pubmed-meshheading:14517297-Cyclin-Dependent Kinase 4,
pubmed-meshheading:14517297-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:14517297-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:14517297-Cyclin-Dependent Kinases,
pubmed-meshheading:14517297-Cyclins,
pubmed-meshheading:14517297-Cycloheximide,
pubmed-meshheading:14517297-Cysteine Endopeptidases,
pubmed-meshheading:14517297-Cysteine Proteinase Inhibitors,
pubmed-meshheading:14517297-Leupeptins,
pubmed-meshheading:14517297-Mice,
pubmed-meshheading:14517297-Models, Biological,
pubmed-meshheading:14517297-Multienzyme Complexes,
pubmed-meshheading:14517297-Precipitin Tests,
pubmed-meshheading:14517297-Proteasome Endopeptidase Complex,
pubmed-meshheading:14517297-Protein Binding,
pubmed-meshheading:14517297-Protein Synthesis Inhibitors,
pubmed-meshheading:14517297-Proto-Oncogene Proteins,
pubmed-meshheading:14517297-RNA, Messenger,
pubmed-meshheading:14517297-Time Factors,
pubmed-meshheading:14517297-Tumor Suppressor Proteins
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pubmed:year |
2003
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pubmed:articleTitle |
P27Kip1 and p21Cip1 are not required for the formation of active D cyclin-cdk4 complexes.
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