title: Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation.
abstract: BACKGROUND
  Microarray studies have shown that the E2F transcription factor influences the expression of many genes but it is unclear how many of these targets are important for E2F-mediated control of cell proliferation.
  
  
  RESULTS
  We assembled a collection of mutant alleles of 44 dE2F1-dependent genes and tested whether these could modify visible phenotypes caused by the tissue-specific depletion of dE2F1. More than half of the mutant alleles dominantly enhanced de2f1-dsRNA phenotypes suggesting that the in vivo functions of dE2F1 can be limited by the reduction in the level of expression of many different targets. Unexpectedly, several mutant alleles suppressed de2f1-dsRNA phenotypes. One of the strongest of these suppressors was Orc5. Depletion of ORC5 increased proliferation in cells with reduced dE2F1 and specifically elevated the expression of dE2F1-regulated genes. Importantly, these effects were independent of dE2F1 protein levels, suggesting that reducing the level of ORC5 did not interfere with the general targeting of dE2F1.
  
  
  CONCLUSIONS
  We propose that the interaction between ORC5 and dE2F1 may reflect a feedback mechanism between replication initiation proteins and dE2F1 that ensures that proliferating cells maintain a robust level of replication proteins for the next cell cycle.
authors.affiliation: Massachusetts General Hospital Cancer Center and Harvard Medical School, Laboratory of Molecular Oncology, Charlestown, MA 02129, USA.
authors.forename: Anabel
authors.initials: A
authors.lastname: Herr
authors.forename: Michelle
authors.initials: M
authors.lastname: Longworth
authors.forename: Jun-Yuan
authors.initials: JY
authors.lastname: Ji
authors.forename: Michael
authors.initials: M
authors.lastname: Korenjak
authors.forename: David M
authors.initials: DM
authors.lastname: Macalpine
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Dyson
mesh_terms: D000483:Alleles; D000818:Animals; D049109:Cell Proliferation; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D050684:E2F Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D051738:Origin Recognition Complex / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D050684:E2F Transcription Factors; C496298:E2f1 protein, Drosophila; D051738:Origin Recognition Complex; D014157:Transcription Factors