p21 functions in a post-mitotic block checkpoint in the apoptotic response to vinblastine |
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Authors: | Anca Bene |
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Institution: | Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA |
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Abstract: | We have shown previously that in KB-3 (HeLa) cells vinblastine causes downregulation of the CDK inhibitor p21 through a c-Jun regulated pathway. To test the hypothesis that p21 downregulation is necessary to alleviate a protective function, we transfected p21 in KB-3 cells and examined the apoptotic response to vinblastine. The results showed that cells overexpressing p21 were apoptosis-resistant, not through an ability of p21 to cause cell cycle arrest prior to mitotic arrest, but through altering the fate of mitotically arrested cells after drug treatment. Moreover, p21 null HCT116 cells were more prone to vinblastine-induced apoptosis relative to wild-type cells. The results provide support for a model whereby p21 downregulation promotes vinblastine-induced apoptosis by alleviating its protective function following mitotic arrest. |
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Keywords: | CDK cyclin-dependent kinase EV empty vector PBS phosphate buffered saline BGS bovine growth serum DMSO dimethyl sulphoxide GAPDH glyceraldehyde-3-phosphate dehydrogenase |
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