Cloning and characterization of mouse E2F8, a novel mammalian E2F family member capable of blocking cellular proliferation.
The E2F transcription factor family plays a crucial and well established role in cell cycle progression. Deregulation of E2F activities in vivo leads to developmental defects and cancer. Based on current evidence in the field, mammalian E2Fs can be functionally categorized into either transcriptional activators (E2F1, E2F2, and E2F3a) or repressors (E2F3b, E2F4, E2F5, E2F6, and E2F7). We have identified a novel E2F family member, E2F8, which is conserved in mice and humans and has its counterpart in Arabidopsis thaliana (E2Ls). Interestingly, E2F7 and E2F8 share unique structural features that distinguish them from other mammalian E2F repressor members, including the presence of two distinct DNA-binding domains and the absence of DP-dimerization, retinoblastoma-binding, and transcriptional activation domains. Similar to E2F7, overexpression of E2F8 significantly slows down the proliferation of primary mouse embryonic fibroblasts. These observations, together with the fact that E2F7 and E2F8 can homodimerize and are expressed in the same adult tissues, suggest that they may have overlapping and perhaps synergistic roles in the control of cellular proliferation.
Maiti
Baidehi
B
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and Department of Molecular Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA.
Li
Jing
J
de Bruin
Alain
A
Gordon
Faye
F
Timmers
Cynthia
C
Opavsky
Rene
R
Patil
Kaustubha
K
Tuttle
John
J
Cleghorn
Whitney
W
Leone
Gustavo
G
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular / Q000379:methods*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D019281:Dimerization; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050704:E2F4 Transcription Factor; D050700:E2F5 Transcription Factor; D050701:E2F6 Transcription Factor; D050702:E2F7 Transcription Factor; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D015723:Gene Library; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D050703:E2F2 Transcription Factor; C493761:E2F2 protein, human; D050704:E2F4 Transcription Factor; C493762:E2F4 protein, human; D050700:E2F5 Transcription Factor; D050701:E2F6 Transcription Factor; D050702:E2F7 Transcription Factor; C493754:E2f1 protein, mouse; C493763:E2f4 protein, mouse; D014157:Transcription Factors