Transient accumulation of retinoblastoma/E2F-1 protein complexes correlates with the onset of neuronal differentiation in the developing quail neural retina.
Retinoblastoma (Rb) protein has been implicated in the control of cell proliferation and malignant transformation in different cell types. To analyze its role as a promoter of cell growth arrest during development, we have studied the temporal pattern of Rb expression and its association with E2F-1 during embryogenesis of the quail neuroretina. During development of this neural organ, most cells stop dividing and begin to differentiate at embryonic days E6 and E7, as indicated by the decline of cyclin-dependent kinase cdk2 and by an increased level of cdk5. At this stage, we observed a shift of hyperphosphorylated Rb protein to its hypophosphorylated form as well as a decrease of the total level of Rb. The Rb-related protein, p107, is also progressively down-regulated from the E7 stage onwards. P130 levels, on the other hand, actually increase. Moreover, cell cycle exit at E6-E7 is characterized by a sudden and transient rise of the E2F-1/RB complex followed by the appearance of the E2F-4/p130 complex starting at E8. Conversely, expression of adenovirus E1A protein in E6 neuroretina cells leads to a dissociation of E2F-1/Rb complex and suppression of cell growth arrest and differentiation. This suggests that cell cycle exit and re-entry may depend on Rb/E2F-1 interaction. Although the rate of Rb synthesis declines in postmitotic cells, as suggested by in vivo metabolic labeling of the Rb protein, the level of the Rb transcript remains
Kastner
A
A
Laboratoire de Biologie Moléculaire et Cellulaire, UMR49 CNRS, Ecole Normale Supérieure de Lyon, France.
Espanel
X
X
Brun
G
G
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D003370:Coturnix; D046508:Culture Techniques; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D016161:Genes, Retinoblastoma; D009474:Neurons / Q000166:cytology*; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050717:Retinoblastoma-Like Protein p130; D050680:Transcription Factor DP1; D014157:Transcription Factors