E2F1 is crucial for E2F-dependent apoptosis.
Loss of the retinoblastoma protein, pRB, leads to apoptosis, and several results have suggested that this is dependent on the E2F transcription factors. However, so far, the ability of the different E2F family members to contribute to apoptosis is controversial. Here, we show that ectopic expression of E2F3 results in apoptosis in both primary mouse fibroblasts and transgenic mice. Apoptosis induced by E2F3 is associated with the accumulation of E2F1 and, strikingly, we found that E2F3-induced apoptosis is dependent on E2F1. On the basis of these results, we propose that the accumulation of crucial levels of E2F1 activity, and not total E2F activity, is essential for the induction of apoptosis in response to a deregulated pRB pathway. These results are consistent with previous findings that E2F1, but not other E2Fs, can have tumour-suppressing activities.
Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy.
Eros
E
Lazzerini Denchi
Kristian
K
Helin
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D005347:Fibroblasts / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53