Document Detail


Identification of pathways regulating cell size and cell-cycle progression by RNAi.
MedLine Citation:
PMID:  16496002     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 organs. 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, p38betaMAPK, 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.
Authors:
Mikael Björklund; Minna Taipale; Markku Varjosalo; Juha Saharinen; Juhani Lahdenperä; Jussi Taipale
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature     Volume:  439     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-23     Completed Date:  2006-03-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  1009-13     Citation Subset:  IM    
Affiliation:
Molecular and Cancer Biology Program, Biomedicum Helsinki, PO Box 63 (Haartmaninkatu 8), FI-00014 University of Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus
Animals
Cell Cycle / genetics*
Cell Line
Cell Size
Conserved Sequence / genetics
Drosophila Proteins / genetics*,  metabolism*
Drosophila melanogaster / cytology*,  genetics*,  metabolism
Gene Library
Genes, Insect / genetics
Humans
Phenotype
Phosphorylation
RNA Interference*
Signal Transduction
Chemical
Reg. No./Substance:
0/Drosophila Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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