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

Mol Cell. 2002 May;9(5):1017-29. doi: 10.1016/s1097-2765(02)00522-1.


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.

MeSH terms

  • 3T3 Cells
  • Animals
  • Apoptosis*
  • Binding Sites
  • Cell Cycle Proteins*
  • DNA / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism*
  • Transcription Factors / metabolism*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, mouse
  • NF-kappa B
  • Proto-Oncogene Proteins c-myc
  • Reactive Oxygen Species
  • Transcription Factors
  • DNA
  • Superoxide Dismutase