%0 Journal Article
%T Involvement of an SCFSlmb complex in timely elimination of E2F upon initiation of DNA replication in Drosophila
%A Jean-Karim H¨¦rich¨¦
%A Dan Ang
%A Ethan Bier
%A Patrick H O'Farrell
%J BMC Genetics
%D 2003
%I BioMed Central
%R 10.1186/1471-2156-4-9
%X 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, Slimb and E2F interacted in vitro in a phosphorylation-dependent manner.We have used genetic and physical interactions to identify the G1/S transcription factor E2F as an SCFSlmb target in Drosophila. These results argue that the SCFSlmb ubiquitin ligase directs E2F destruction in S phase.The ubiquitin-proteasome pathway is essential for degradation of many regulatory proteins. Proteins are targeted for proteasome-mediated degradation by attachment of a polyubiquitin chain. The addition of a polyubiquitin chain to a protein requires the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2) and a ubiquitin-protein ligase (E3) [1]. E3 activities are thought to be essential because they are involved in substrate recognition. SCF complexes are E3s composed of the Cullin family member Cul1 (Cdc53 in S. cerevisiae), as well as, Skp1, Roc1 (also called Rbx1 or Hrt1) and one of the numerous F-box proteins that act as a receptor for the substrate (for revi
%U http://www.biomedcentral.com/1471-2156/4/9