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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
1996-2-20
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pubmed:abstractText |
The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and inhibits the kinase activity that is required for cell cycle progression. We investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines and found that WAF1/Cip1 expression was detectable in many of the cell lines, even when mutant p53 was present. We also showed that WAF1/Cip1 protein level was very low in LN-Z308 cells that do not express endogenous p53. Transfection of the wild-type p53 into this cell line activated WAF1/Cip1 expression and inhibited cell growth. In contrast, transfection of the p53 mutant 248Trp failed to activate WAF1/Cip1 expression. Transfection of WAF1/Cip1 alone also inhibited LN-Z308 cell proliferation. However, cotransfection of the p53 mutant 248Trp with WAF1/Cip1 attenuated the growth-suppression effect of WAF1/Cip1. Our analysis with Western blot showed that the levels of cyclin E increased in cells transfected with p53 mutants. We conclude that p53 mutants may counter the negative regulators, such as WAF1/Cip1, by the elevation of positive cell cycle regulators, and the presence of WAF1/Cip1 in tumor cells is not sufficient for growth inhibition.
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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/CDKN1A protein, human,
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/Enzyme Inhibitors
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1044-9523
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
909-13
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8547219-Brain Neoplasms,
pubmed-meshheading:8547219-Cell Cycle,
pubmed-meshheading:8547219-Cell Division,
pubmed-meshheading:8547219-Cyclin-Dependent Kinase Inhibitor p21,
pubmed-meshheading:8547219-Cyclin-Dependent Kinases,
pubmed-meshheading:8547219-Cyclins,
pubmed-meshheading:8547219-Enzyme Inhibitors,
pubmed-meshheading:8547219-Genes, p53,
pubmed-meshheading:8547219-Glioblastoma,
pubmed-meshheading:8547219-Humans,
pubmed-meshheading:8547219-Mutation,
pubmed-meshheading:8547219-Transfection,
pubmed-meshheading:8547219-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Inhibition of human glioblastoma cell growth by WAF1/Cip1 can be attenuated by mutant p53.
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pubmed:affiliation |
Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, 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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