Myc requires distinct E2F activities to induce S phase and apoptosis.
Previous work has shown that the Myc transcription factor induces transcription of the E2F1, E2F2, and E2F3 genes. Using primary mouse embryo fibroblasts deleted for individual E2F genes, we now show that Myc-induced S phase and apoptosis requires distinct E2F activities. The ability of Myc to induce S phase is impaired in the absence of either E2F2 or E2F3 but not E2F1 or E2F4. In contrast, the ability of Myc to induce apoptosis is markedly reduced in cells deleted for E2F1 but not E2F2 or E2F3. From this data, we propose that the induction of specific E2F activities is an essential component in the Myc pathways that control cell proliferation and cell fate decisions.
Leone
G
G
Division of Human Cancer Genetics, Department of Molecular Virology, Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
Sears
R
R
Huang
E
E
Rempel
R
R
Nuckolls
F
F
Park
C H
CH
Giangrande
P
P
Wu
L
L
Saavedra
H I
HI
Field
S J
SJ
Thompson
M A
MA
Yang
H
H
Fujiwara
Y
Y
Greenberg
M E
ME
Orkin
S
S
Smith
C
C
Nevins
J R
JR
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; D005347:Fibroblasts / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050699:E2F3 Transcription Factor; D050704:E2F4 Transcription Factor; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors