Reference Report

Reference
Citation	Shibutani, S.T., de la Cruz, A.F.A., Tran, V., Turbyfill, W.J., Reis, T., Edgar, B.A., Duronio, R.J. (2008). Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev. Cell 15(6): 890--900. (Export to RIS)
FlyBase ID	FBrf0206613
Publication Type	Research paper
PubMed ID	19081076
PubMed Abstract	E2F transcription factors are key regulators of cell proliferation that are inhibited by pRb family tumor suppressors. pRb-independent modes of E2F inhibition have also been described, but their contribution to animal development and tumor suppression is unclear. Here, we show that S phase-specific destruction of Drosophila E2f1 provides a novel mechanism for cell cycle regulation. E2f1 destruction is mediated by a PCNA-interacting-protein (PIP) motif in E2f1 and the Cul4(Cdt2) E3 ubiquitin ligase and requires the Dp dimerization partner but not direct Cdk phosphorylation or Rbf1 binding. E2f1 lacking a functional PIP motif accumulates inappropriately during S phase and is more potent than wild-type E2f1 at accelerating cell cycle progression and inducing apoptosis. Thus, S phase-coupled destruction is a key negative regulator of E2f1 activity. We propose that pRb-independent inhibition of E2F during S phase is an evolutionarily conserved feature of the metazoan cell cycle that is necessary for development.
DOI	10.1016/j.devcel.2008.10.003
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Dev. Cell
Title	Developmental Cell
Publication Year	2001-
ISBN/ISSN
Data from Reference
Alleles (8)
	E2f^{PIP-3A.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-7A.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{PIP-7del.Scer\UAS.P\T.T:Avic\GFP-EGFP} E2f^{Scer\UAS.P\T.T:Avic\GFP-EGFP} Scer\GAL4^arm.PS Scer\GAL4^en-e16E Scer\GAL4^prd.RG1 T:Avic\GFP^EGFP
Constructs (6)
	P{GAL4-arm.S} P{GAL4-prd.F} P{UASp-GFP-E2f1.PIP-3A} P{UASp-GFP-E2f1.PIP-7A} P{UASp-GFP-E2f1.PIP-7del} P{UASp-GFP-E2f1.WT}
Genes (14)
	ago Cul-4 Dp E2f l(2)dtl lin19 mus209 pic Rbf RnrS Scer\GAL4 Skp2 skpA slmb
Insertions (1)
	P{en2.4-GAL4}e16E
Natural transposons (1)
	P-element