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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
23
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pubmed:dateCreated |
2011-6-10
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pubmed:abstractText |
The small GTPase Rac1 is involved in the activation of the reduced NAD phosphate oxidase complex resulting in superoxide production. We recently showed that Bcl-2 overexpression inhibited apoptosis in leukemia cells by creating a pro-oxidant intracellular milieu, and that inhibiting intracellular superoxide production sensitized Bcl-2-overexpressing cells to apoptotic stimuli. We report here that silencing and functional inhibition of Rac1 block Bcl-2-mediated increase in intracellular superoxide levels in tumor cells. Using confocal, electron microscopy and coimmunoprecipitation, as well as glutathione S-transferase-fusion proteins, we provide evidence for a colocalization and physical interaction between the 2 proteins. This interaction is blocked in vitro and in vivo by the BH3 mimetics as well as by synthetic Bcl-2 BH3 domain peptides. That this interaction is functionally relevant is supported by the ability of the Bcl-2 BH3 peptide as well as the silencing and functional inhibition of Rac1 to inhibit intracellular superoxide production as well as overcome Bcl-2-mediated drug resistance in human leukemia cells and cervical cancer cells. Notably, the interaction was observed in primary cells derived from patients with B-cell lymphoma overexpressing Bcl-2 but not in noncancerous tissue. These data provide a novel facet in the biology of Bcl-2 with potential implications for targeted anticancer drug design.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein (53-86),
http://linkedlifedata.com/resource/pubmed/chemical/Neuropeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptidomimetics,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RAC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Rac1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Rac1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1528-0020
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6214-26
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pubmed:meshHeading |
pubmed-meshheading:21474673-Animals,
pubmed-meshheading:21474673-Apoptosis,
pubmed-meshheading:21474673-Gene Silencing,
pubmed-meshheading:21474673-HeLa Cells,
pubmed-meshheading:21474673-Humans,
pubmed-meshheading:21474673-Jurkat Cells,
pubmed-meshheading:21474673-Mice,
pubmed-meshheading:21474673-NIH 3T3 Cells,
pubmed-meshheading:21474673-Neoplasms,
pubmed-meshheading:21474673-Neuropeptides,
pubmed-meshheading:21474673-Peptide Fragments,
pubmed-meshheading:21474673-Peptidomimetics,
pubmed-meshheading:21474673-Protein Binding,
pubmed-meshheading:21474673-Proto-Oncogene Proteins,
pubmed-meshheading:21474673-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:21474673-Rats,
pubmed-meshheading:21474673-Superoxides,
pubmed-meshheading:21474673-rac GTP-Binding Proteins,
pubmed-meshheading:21474673-rac1 GTP-Binding Protein
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pubmed:year |
2011
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pubmed:articleTitle |
The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity.
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pubmed:affiliation |
Department of Physiology, Yong Loo Lin School of Medicine, Singapore.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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