Source:http://linkedlifedata.com/resource/pubmed/id/19324082
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2009-4-27
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| pubmed:abstractText |
In this work we report evidences of a functional relationship between C3G and p38 MAPK in the apoptotic effect of STI-571 on the chronic myeloid leukemia (CML) cell line K562. This has been demonstrated by knocking down C3G and p38alpha using the interfering RNA approach, as well as through targeting p38 by its inhibitor SB203580. The results indicate that p38 is a mediator of the STI-571-induced apoptosis, while C3G plays a negative role on STI-571-mediated p38 activation through a Rap1-dependent mechanism. According to this, gene expression analysis in C3G silenced cells revealed an upregulation of a large number of genes involved in apoptosis. Some of these genes are also down-regulated (at the protein level) upon p38alpha knock-down, which further suggests a functional association between these two proteins. On the other hand, C3G knock-down reverts the STI-571-inhibitory effect on ERKs and Akt pathways in a Rap1-independent fashion. Moreover, C3G overexpression also increased both, basal and STI-571-induced apoptosis, in agreement with previous reports. Therefore, our results strongly suggest a dual regulatory role for C3G in CML cells, modulating both apoptosis and survival via Rap-dependent and independent mechanisms.
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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/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide-Releasing...,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/imatinib,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1873-3913
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1229-35
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:19324082-Antineoplastic Agents,
pubmed-meshheading:19324082-Apoptosis,
pubmed-meshheading:19324082-Cell Survival,
pubmed-meshheading:19324082-Enzyme Activation,
pubmed-meshheading:19324082-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19324082-Gene Silencing,
pubmed-meshheading:19324082-Guanine Nucleotide-Releasing Factor 2,
pubmed-meshheading:19324082-Humans,
pubmed-meshheading:19324082-Immunoblotting,
pubmed-meshheading:19324082-K562 Cells,
pubmed-meshheading:19324082-Leukemia, Myelogenous, Chronic, BCR-ABL Positive,
pubmed-meshheading:19324082-Models, Biological,
pubmed-meshheading:19324082-Piperazines,
pubmed-meshheading:19324082-Pyrimidines,
pubmed-meshheading:19324082-Signal Transduction,
pubmed-meshheading:19324082-Transcription, Genetic,
pubmed-meshheading:19324082-p38 Mitogen-Activated Protein Kinases,
pubmed-meshheading:19324082-rap1 GTP-Binding Proteins
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| pubmed:year |
2009
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| pubmed:articleTitle |
C3G silencing enhances STI-571-induced apoptosis in CML cells through p38 MAPK activation, but it antagonizes STI-571 inhibitory effect on survival.
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| pubmed:affiliation |
Centro de Investigación del Cáncer, IBMCC, Universidad de Salamanca-CSIC, Salamanca, Spain.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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