Functional genomics identifies TOR-regulated genes that control growth and division
David A Guertin1, Kalyani V P Guntur, George W Bell
1Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Current Biology : CB
|May 23, 2006
Summary
Researchers identified genes controlling cell growth by inhibiting the target of rapamycin (TOR) pathway in Drosophila. Many identified genes are conserved in mammals and linked to human diseases, highlighting TOR
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The target of rapamycin (TOR) kinase is a key regulator of eukaryotic cell growth.
- TOR signaling is targeted by the drug rapamycin, but downstream genes controlling growth in higher eukaryotes are not well understood.
Purpose of the Study:
- To identify genes regulated by Drosophila TOR (dTOR) that control cell size.
- To investigate the conservation and potential disease relevance of dTOR-regulated genes in mammals.
Main Methods:
- Used a combination of rapamycin inhibition, transcriptional profiling, and RNA interference in Drosophila tissue culture cells.
- Analyzed gene expression changes in response to dTOR inhibition.
Main Results:
- Identified several genes regulated by dTOR that control cell size, with some also involved in cell division.
- Found that most identified genes are conserved in mammals, with some linked to human diseases.
- Discovered that dTOR-regulated genes are enriched for ribosome biogenesis regulators and identified conserved roles for CG3071/SAW and CG6677/ASH2L in TOR-dependent growth.
Conclusions:
- Combining RNA interference with transcriptional profiling is an effective strategy for identifying genes involved in specific biological processes.
- This approach, applied in model organisms, can successfully identify evolutionarily conserved genes with functions in mammals, including those relevant to human disease.
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