Identification of pathways regulating cell size and cell-cycle progression by RNAi
Open Access
- 1 February 2006
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 439 (7079), 1009-1013
- https://doi.org/10.1038/nature04469
Abstract
Many high-throughput loss-of-function analyses of the eukaryotic cell cycle have relied on the unicellular yeast species Saccharomyces cerevisiae and Schizosaccharomyces pombe. In multicellular organisms, however, additional control mechanisms regulate the cell cycle to specify the size of the organism and its constituent organs1. To identify such genes, here we analysed the effect of the loss of function of 70% of Drosophila genes (including 90% of genes conserved in human) on cell-cycle progression of S2 cells using flow cytometry. To address redundancy, we also targeted genes involved in protein phosphorylation simultaneously with their homologues. We identify genes that control cell size, cytokinesis, cell death and/or apoptosis, and the G1 and G2/M phases of the cell cycle. Classification of the genes into pathways by unsupervised hierarchical clustering on the basis of these phenotypes shows that, in addition to classical regulatory mechanisms such as Myc/Max, Cyclin/Cdk and E2F, cell-cycle progression in S2 cells is controlled by vesicular and nuclear transport proteins, COP9 signalosome activity and four extracellular-signal-regulated pathways (Wnt, p38βMAPK, FRAP/TOR and JAK/STAT). In addition, by simultaneously analysing several phenotypes, we identify a translational regulator, eIF-3p66, that specifically affects the Cyclin/Cdk pathway activity.Keywords
This publication has 29 references indexed in Scilit:
- Genome-wide survey of protein kinases required for cell cycle progressionNature, 2004
- Cell-cycle checkpoints and cancerNature, 2004
- Parallel Chemical Genetic and Genome-Wide RNAi Screens Identify Cytokinesis Inhibitors and TargetsPLoS Biology, 2004
- Negative Regulation of dE2F1 by Cyclin-Dependent Kinases Controls Cell Cycle TimingCell, 2004
- Genome-Wide RNAi Analysis of Growth and Viability in Drosophila CellsScience, 2004
- Recycling the Cell CycleCell, 2004
- A functional genomic screen for cardiogenic genes using RNA interference in developing Drosophila embryosProceedings of the National Academy of Sciences of the United States of America, 2003
- Identification of Hedgehog Pathway Components by RNAi in Drosophila Cultured CellsScience, 2003
- How the Cyclin Became a Cyclin: Regulated Proteolysis in the Cell CycleCell, 1999
- Size Control in Animal DevelopmentCell, 1999