Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of Rb.
The Rb/E2F pathway plays a critical role in the control ofcellular proliferation. Here, we report that E2F1, E2F2, and E2F3 make major individual contributions toward the in vivo phenotypic consequences of Rb deficiency. In the developing lens of Rb(-/-) embryos, loss of E2F1, E2F2, or E2F3 reduces the unscheduled proliferation of fiber cells, with the loss of E2F3 having the most pronounced effect. In Rb-deficient retinas, all three E2Fs contribute equally to the ectopic proliferation of postmitotic neuronal cells. In contrast, E2F1 is unique in mediating apoptosis in both Rb(-/-) lenses and retinas. In the central nervous system, loss of E2F1 or E2F3 can almost completely eliminate the ectopic DNA replication and apoptosis observed in Rb(-/-) embryos, and loss of E2F2 partially reduces the unscheduled DNA replication and has no effect on apoptosis. These results provide clear evidence for functional specificity among E2Fs in the control of Rb-dependent proliferation and apoptosis in a tissue-specific manner.
Saavedra
Harold I
HI
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and Department of Molecular Genetics, The Ohio State University, Columbus 43210, USA.
Wu
Lizhao
L
de Bruin
Alain
A
Timmers
Cynthia
C
Rosol
Thomas J
TJ
Weinstein
Michael
M
Robinson
Michael L
ML
Leone
Gustavo
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D005260:Female; D005313:Fetal Death; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D016160:Retinoblastoma Protein / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; C493754:E2f1 protein, mouse; C490840:E2f3 protein, mouse; D016160:Retinoblastoma Protein; D014157:Transcription Factors