E2F1 and c-Myc potentiate apoptosis through inhibition of NF-κB activity that facilitates MnSOD-mediated ROS elimination

被引:256
作者
Tanaka, H
Matsumura, I
Ezoe, S
Satoh, Y
Sakamaki, T
Albanese, C
Machii, T
Pestell, RG
Kanakura, Y
机构
[1] Osaka Univ, Grad Sch Med, Dept Hematol Oncol, Suita, Osaka 5650871, Japan
[2] Fdn Biomed Res & Innovat, Chuo Ku, Kobe, Hyogo 6508543, Japan
[3] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Dev & Mol Biol, Bronx, NY 10461 USA
[4] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
关键词
D O I
10.1016/S1097-2765(02)00522-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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-kappaB in mock-transfected NIH3T3, while this induction was inhibited in NIH3T3 overexpressing c-Myc or E2F1. In these clones, E2F1 inhibited NF-kappaB 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-kappaB 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-kappaB activity.
引用
收藏
页码:1017 / 1029
页数:13
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