Direct coupling of the cell cycle and cell death machinery by E2F.
Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.
Nahle
Zaher
Z
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Polakoff
Julia
J
Davuluri
Ramana V
RV
McCurrach
Mila E
ME
Jacobson
Matthew D
MD
Narita
Masashi
M
Zhang
Michael Q
MQ
Lazebnik
Yuri
Y
Bar-Sagi
Dafna
D
Lowe
Scott W
SW
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D018899:CpG Islands; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017500:Adenovirus E1A Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D012313:RNA; D045304:Cytochromes c; D008156:Luciferases; D020169:Caspases