Source:http://linkedlifedata.com/resource/pubmed/id/20837141
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-10-18
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pubmed:abstractText |
p27(Kip1) is a cyclin-dependent kinase inhibitor that plays a critical role in regulating G(1)/S transition, and whose activity is, in part, regulated through interactions with D-type cyclins. We have generated the BD1-9 cell line, a BaF3 pro-B cells derivative in which cyclin D1 can be induced rapidly and reversibly by ponasterone A. The induction of cyclin D1 expression leads to a targeted p27(Kip1) accumulation in both cytoplasmic and nuclear compartments. But, only the p27(Kip1) form phosphorylated on serine 10 (pSer10-p27(Kip1)) accumulates in BD1-9 cells. We found that the binding of cyclin D1 and pSer10-p27(Kip1) prevents p27(Kip1) degradation by the cytoplasmic Kip1 ubiquitylation-promoting complex (KPC) proteosomic pathway. Importantly, the nuclear CDK2 activity which is crucial for G(1)/S transition is not altered by p27(Kip1) increase. Using siRNA techniques, we revealed that p27(Kip1) inhibition does not affect the distribution of BD1-9 cells in the different phases of the cell cycle. Our study demonstrates that aberrant cyclin D1 expression acts as a p27(Kip1) trap in B lymphocytes but does not induce p27(Kip1) relocation from the nucleus to the cytoplasm and does not modulate the G(1)/S transition. Since our cellular model mimics what observed in aggressive lymphomas, our data bring new insights into the understanding of their physiopathology.
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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/Cyclin D1,
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/Ecdysterone,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/ponasterone A
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1873-3913
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pubmed:author | |
pubmed:copyrightInfo |
Copyright © 2010 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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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 |
171-9
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pubmed:meshHeading |
pubmed-meshheading:20837141-Animals,
pubmed-meshheading:20837141-Cell Line,
pubmed-meshheading:20837141-Cyclin D1,
pubmed-meshheading:20837141-Cyclin-Dependent Kinase 4,
pubmed-meshheading:20837141-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:20837141-Ecdysterone,
pubmed-meshheading:20837141-G1 Phase,
pubmed-meshheading:20837141-Mice,
pubmed-meshheading:20837141-Phosphorylation,
pubmed-meshheading:20837141-Precursor Cells, B-Lymphoid,
pubmed-meshheading:20837141-Protein Stability,
pubmed-meshheading:20837141-RNA, Small Interfering,
pubmed-meshheading:20837141-RNA Interference,
pubmed-meshheading:20837141-S Phase
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pubmed:year |
2011
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pubmed:articleTitle |
Cyclin D1 regulates p27(Kip1) stability in B cells.
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pubmed:affiliation |
Biologie Moléculaire et Cellulaire de la Signalisation, EA 3919, IFR ICORE, Université de Caen Basse-Normandie, Caen Cedex, France. sophie.bustany@aliceadsl.fr
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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