Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila

BMC Genetics
Jean-Karim HérichéP H O'Farrell

Abstract

Cul1 is a core component of the evolutionarily conserved SCF-type ubiquitin ligases that target specific proteins for destruction. SCF action contributes to cell cycle progression but few of the key targets of its action have been identified. We found that expression of the mouse Cul1 (mCul1) in the larval wing disc has a dominant negative effect. It reduces, but does not eliminate, the function of SCF complexes, promotes accumulation of Cubitus interruptus (a target of SCF action), triggers apoptosis, and causes a small wing phenotype. A screen for mutations that dominantly modify this phenotype showed effective suppression upon reduction of E2F function, suggesting that compromised downregulation of E2F contributes to the phenotype. Partial inactivation of Cul1 delayed the abrupt loss of E2F immunofluorescence beyond its normal point of downregulation at the onset of S phase. Additional screens showed that mild reduction in function of the F-box encoding gene slimb enhanced the mCul1 overexpression phenotype. Cell cycle modulation of E2F levels is virtually absent in slimb mutant cells in which slimb function is severely reduced. This implicates Slimb, a known targeting subunit of SCF, in E2F downregulation. In addition, Slim...Continue Reading

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Citations

Nov 23, 2012·Cell Death & Disease·S BhutaniN R Jana
Nov 1, 2011·Nature·Norman ZielkeBruce A Edgar
Mar 31, 2005·Molecular and Cellular Biology·Maxim V FrolovNicholas J Dyson
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Jun 19, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Yan ZhouYang Yao
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Feb 22, 2005·Archives of Oral Biology·Isabelle MiletichPaul T Sharpe

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Methods Mentioned

BETA
ubiquitination
transgenic
genetic modification
pull-down
transfection
dissection

Software Mentioned

DeltaVision
Slimb

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis