Source:http://linkedlifedata.com/resource/pubmed/id/15467449
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
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| pubmed:dateCreated |
2004-12-21
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| pubmed:abstractText |
The functional significance of the cyclin-dependent kinase inhibitor (CDKI) p21(Cip1/WAF1) in paclitaxel-mediated lethality was examined in p53-null human leukemia cells (U937 and Jurkat). In these cells, paclitaxel exposure failed to induce p21(Cip1/Waf1) expression. Nevertheless, stable expression of U937 cells with a p21(Cip1/WAF1) antisense construct blocked paclitaxel-induced G(2)M arrest and increased mitochondrial injury, caspase activation, apoptosis, and loss of clonogenic potential. Consistent with these results, enforced expression of p21(Cip1/WAF1) in Jurkat cells increased the percentage of cells arrested in G2M and attenuated paclitaxel-mediated mitochondrial injury and apoptosis. Unexpectedly, enforced expression of p21(Cip1/WAF1) diminished paclitaxel-mediated inactivation of ERK, and reduced paclitaxel-induced activation of JNK as well as Bcl-2 phosphorylation. Together, these findings suggest that p21(Cip1/WAF1) partially protects p53-null human leukemia cells from paclitaxel-mediated lethality, and raise the possibility that p21(Cip1/WAF1)-associated perturbations in signal transduction pathways as well as Bcl-2 phosphorylation status may play a role in this phenomenon.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antisense Elements (Genetics),
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Doxycycline,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1551-4005
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
3
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1305-11
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15467449-Antisense Elements (Genetics),
pubmed-meshheading:15467449-Apoptosis,
pubmed-meshheading:15467449-Cell Cycle,
pubmed-meshheading:15467449-Cell Division,
pubmed-meshheading:15467449-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:15467449-Doxycycline,
pubmed-meshheading:15467449-Flow Cytometry,
pubmed-meshheading:15467449-G2 Phase,
pubmed-meshheading:15467449-Humans,
pubmed-meshheading:15467449-Jurkat Cells,
pubmed-meshheading:15467449-Leukemia,
pubmed-meshheading:15467449-Membrane Potentials,
pubmed-meshheading:15467449-Mitochondria,
pubmed-meshheading:15467449-Mitotic Index,
pubmed-meshheading:15467449-Paclitaxel,
pubmed-meshheading:15467449-Tetradecanoylphorbol Acetate,
pubmed-meshheading:15467449-Tumor Suppressor Protein p53,
pubmed-meshheading:15467449-U937 Cells
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| pubmed:year |
2004
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| pubmed:articleTitle |
The cyclin-dependent kinase inhibitor p21(CIP1/WAF1) blocks paclitaxel-induced G2M arrest and attenuates mitochondrial injury and apoptosis in p53-null human leukemia cells.
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| pubmed:affiliation |
Department of Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia 23298, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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