Abstract
The knockdown of Pim-1 or inhibition of Pim-1 activity significantly increased γ-H2A.X expression. The effect was correlated to apoptosis and was attributed to the inhibition of nonhomologous DNA-end-joining (NHEJ) repair activity supported by the following observations: (1) inhibition of ATM and DNA-PKcs activities, (2) down-regulation of Ku expression and nuclear localization and (3) decrease of DNA end-binding of both Ku70 and Ku80. The data suggest that Pim-1 plays a crucial role in the regulation of NHEJ repair. In the absence of Pim-1, the ability of DNA repair significantly decreases when exposed to paclitaxel, leading to severe DNA damage and apoptosis.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / genetics
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Cell Line, Tumor
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Cell Proliferation / drug effects
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DNA End-Joining Repair / drug effects*
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DNA Helicases / metabolism
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DNA-Binding Proteins / metabolism
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Drug Resistance, Neoplasm / drug effects
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Gene Knockdown Techniques
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Histones / genetics*
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Humans
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Ku Autoantigen
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Male
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Microtubules / genetics
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Paclitaxel / pharmacology*
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Prostatic Neoplasms / drug therapy
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Prostatic Neoplasms / genetics*
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Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors
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Proto-Oncogene Proteins c-pim-1 / genetics*
Substances
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DNA-Binding Proteins
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H2AX protein, human
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Histones
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PIM1 protein, human
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Proto-Oncogene Proteins c-pim-1
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DNA Helicases
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XRCC5 protein, human
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Ku Autoantigen
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Paclitaxel