Reference Report

Reference
Citation	Davidson, J.M., Duronio, R.J. (2012). S phase-coupled e2f1 destruction ensures homeostasis in proliferating tissues. PLoS Genet. 8(8): e1002831. (Export to RIS)
FlyBase ID	FBrf0219273
Publication Type	Research paper
PubMed ID	22916021
PubMed Abstract	Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila activator E2F (E2f1) to explore the developmental requirement for S phase-coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle progression, because a stable E2f1 mutant that cannot function as a transcription factor or drive cell cycle progression also triggers apoptosis. This observation suggests that the inappropriate presence of E2f1 protein during S phase can trigger apoptosis by mechanisms that are independent of E2F acting directly at target genes. The ability of S phase-stabilized E2f1 to trigger apoptosis requires an interaction between E2f1 and the Drosophila pRb homolog, Rbf1, and involves induction of the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of apoptosis results in tissue overgrowth and lethality. We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues.
DOI	10.1371/journal.pgen.1002831
Related Publication(s)
Note	It's all in the timing: too much E2F is a bad thing. Nicolay and Dyson, 2012, PLoS Genet. 8(8): e1002909 [FBrf0220291]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	PLoS Genet.
Title	PLoS Genetics
Publication Year	2005-
ISBN/ISSN	1553-7404 1553-7390
Data from Reference
Aberrations (1)
	Df(3L)H99
Alleles (16)
	Avic\GFP^Scer\UAS.cUa BacA\p35^Scer\UAS.cHa Disc\RFP^Scer\UAS.cWa E2f^{336-805.Scer\UAS.T:Ivir\HA1} E2f^{DBD.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-3A.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-3A-DBD.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-3A-Rb.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-3A-Trunc.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{Rb.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{Trunc.Scer\UAS.P\T.T:Avic\GFP-EGFP} Scer\GAL4^en-e16E Scer\GAL4^GMR.PU T:Avic\GFP^EGFP W⁰⁵⁰¹⁴
Constructs (13)
	P{GMR-GAL4.U} P{UAS-GFP.U} P{UAS-HA-E2f.336-805} P{UAS-p35.H} P{UASp-GFP-E2f1.PIP-3A} P{UASp-GFP-E2f1.WT} P{UASp-GFP-E2f.DBD} P{UASp-GFP-E2f.PIP-3A-DBD} P{UASp-GFP-E2f.PIP-3A-Rb} P{UASp-GFP-E2f.PIP-3A-Trunc} P{UASp-GFP-E2f.Rb} P{UASp-GFP-E2f.Trunc} P{UAS-RFP.W}
Genes (11)
	Avic\GFP BacA\p35 Disc\RFP Dp E2f grim RnrS rpr Scer\GAL4 T:Ivir\HA1 W
Insertions (2)
	P{en2.4-GAL4}e16E P{PZ}W⁰⁵⁰¹⁴
Natural transposons (1)
	P-element