title: E2f2 induces cone photoreceptor apoptosis independent of E2f1 and E2f3.
abstract: The 'activating' E2fs (E2f1-3) are transcription factors that potently induce quiescent cells to divide. Work on cultured fibroblasts suggested they were essential for division, but in vivo analysis in the developing retina and other tissues disproved this notion. The retina, therefore, is an ideal location to assess other in vivo adenovirus E2 promoter binding factor (E2f) functions. It is thought that E2f1 directly induces apoptosis, whereas other activating E2fs only induce death indirectly by upregulating E2f1 expression. Indeed, mouse retinoblastoma (Rb)-null retinal neuron death requires E2f1, but not E2f2 or E2f3. However, we report an entirely distinct mechanism in dying cone photoreceptors. These neurons survive Rb loss, but undergo apoptosis in the cancer-prone retina lacking both Rb and its relative p107. We show that while E2f1 killed Rb/p107 null rod, bipolar and ganglion neurons, E2f2 was required and sufficient for cone death, independent of E2f1 and E2f3. Moreover, whereas E2f1-dependent apoptosis was p53 and p73-independent, E2f2 caused p53-dependent cone death. Our in vivo analysis of cone photoreceptors provides unequivocal proof that E2f-induces apoptosis independent of E2f1, and reveals distinct E2f1- and E2f2-activated death pathways in response to a single tumorigenic insult.
authors.affiliation: Department of Ophthalmology and Visual Science, Toronto Western Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Forrest
authors.forename: R
authors.initials: R
authors.lastname: Bremner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050687:E2F1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050703:E2F2 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050699:E2F3 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012160:Retina / Q000473:pathology / Q000503:physiopathology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology* / Q000502:physiology; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050720:Retinoblastoma-Like Protein p107 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; D050699:E2F3 Transcription Factor; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
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