Caspase-dependent apoptosis by ectopic expression of E2F-4.
E2F is a family of transcription factors which regulates cell cycle and apoptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentially bind pRb, while E2F-4 and 5 have no nuclear localization signal and preferentially bind p107/p130. E2F-6 suppresses the transcriptional activity of other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F protein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-1 and E2F-4 on cell cycle progression and apoptosis in Chinese hamster cell lines. We found that E2F-4, as well as DP-1 and E2F-1, induced growth arrest and caspase-dependent apoptosis. E2F-4 did not have a marked effect on cell cycle progression, while E2F-1 induced DNA synthesis of resting cells and DP-1 arrested cells in G1. Ectopic expression of E2F-4 did not activate E2F-dependent transcription. Our results suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 and DP-1.
Chang
Y C
YC
Department of Pathology, University of Vermont College of Medicine, Burlington 05403, USA.
Nakajima
H
H
Illenye
S
S
Lee
Y S
YS
Honjo
N
N
Makiyama
T
T
Fujiwara
I
I
Mizuta
N
N
Sawai
K
K
Saida
K
K
Mitsui
Y
Y
Heintz
N H
NH
Magae
J
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016466:CHO Cells; D002352:Carrier Proteins; D020169:Caspases / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D050701:E2F6 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D013752:Tetracycline / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050704:E2F4 Transcription Factor; D050701:E2F6 Transcription Factor; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors; D020169:Caspases; D013752:Tetracycline