E2F1 and c-Myc Potentiate Apoptosis through Inhibition of NF-κB Activity that Facilitates MnSOD-Mediated ROS Elimination

来自 dx.doi.org

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作者：

H Tanaka，I Matsumura，S Ezoe，Y Satoh，Y Kanakura

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摘要：

Overexpression of c-Myc or E2F1 sensitizes host cells to various types of apoptosis. Here, we found that overexpressed c-Myc or E2F1 induces accumulation of reactive oxygen species (ROS) and thereby enhances serum-deprived apoptosis in NIH3T3 and Saos-2. During serum deprivation, MnSOD mRNA was induced by NF-κB in mock-transfected NIH3T3, while this induction was inhibited in NIH3T3 overexpressing c-Myc or E2F1. In these clones, E2F1 inhibited NF-κB activity by binding to its subunit p65 in competition with a heterodimeric partner p50. In addition to overexpressed E2F1, endogenous E2F1 released from Rb was also found to inhibit NF-κB activity in a cell cycle-dependent manner by using E2F1 +/+ and E2F1 −/− murine embryonic fibroblasts. These results indicate that E2F1 promotes apoptosis by inhibiting NF-κB activity.

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关键词：

Animals Mice 3T3 Cells Reactive Oxygen Species Superoxide Dismutase Transcription Factors DNA DNA-Binding Proteins NF-kappa B Proto-Oncogene Proteins c-myc