RRC ID 21861
著者 Herr A, Longworth M, Ji JY, Korenjak M, Macalpine DM, Dyson NJ.
タイトル Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation.
ジャーナル Dev Dyn
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.
巻・号 241(11)
ページ 1695-707
公開日 2012-11-1
DOI 10.1002/dvdy.23857
PMID 22972499
PMC PMC3760379
MeSH Alleles Animals Cell Proliferation Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* E2F Transcription Factors / genetics E2F Transcription Factors / metabolism* Immunohistochemistry In Situ Hybridization Models, Biological Origin Recognition Complex / genetics Origin Recognition Complex / metabolism Transcription Factors / genetics Transcription Factors / metabolism*
IF 3.275
引用数 2
WOS 分野 ANATOMY & MORPHOLOGY DEVELOPMENTAL BIOLOGY
リソース情報
ショウジョウバエ 7833R-1 7833R-3