Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs.
Previous experiments suggest that a key event in the commitment of cultured mammalian cells to entering S phase is a rise in activity of the transcription factor E2F. In this report, we study the role of Drosophila E2F in imaginal disc cells in vivo, by examining the distribution of the endogenous protein and studying the consequences of ectopic E2F expression. First, we find that endogenous E217 falls from high to very low levels as cells initiate DNA synthesis during a developmentally regulated G1-S-transition in the eye disc. Second, we find that ectopic E2F expression drives many otherwise quiescent cells to enter S phase. Subsequently, cells throughout the discs express reaper (a regulator of apoptosis) and then die. Third, we find that ectopic E2F expression during S phase in normally cycling cells blocks their re-entry into S phase in the following cell cycle. Although we do not know the fate of these cells, we suspect that ultimately they are killed by ectopic E2F. Taken together, our results show that an elevation in the level of E2F is sufficient to induce imaginal disc cells to enter S phase. Furthermore, they suggest that the downregulation of E2F upon entry into S phase may be essential to prevent the induction of apoptosis.
Asano
M
M
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Nevins
J R
JR
Wharton
R P
RP
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000166:cytology* / Q000196:embryology; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D005123:Eye / Q000166:cytology / Q000196:embryology; D016193:G1 Phase; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D007814:Larva; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C088053:Dp transcription factor, Drosophila; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D056465:Retinoblastoma-Binding Protein 1; D015534:Trans-Activators; D014157:Transcription Factors