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Citation
Lindquist, R.A., Ottina, K.A., Wheeler, D.B., Hsu, P.P., Thoreen, C.C., Guertin, D.A., Ali, S.M., Sengupta, S., Shaul, Y.D., Lamprecht, M.R., Madden, K.L., Papallo, A.R., Jones, T.R., Sabatini, D.M., Carpenter, A.E. (2011). Genome-scale RNAi on living-cell microarrays identifies novel regulators of Drosophila melanogaster TORC1-S6K pathway signaling.  Genome Res. 21(3): 433--446.
FlyBase ID
FBrf0213199
Publication Type
Research paper
Abstract
The evolutionarily conserved target of rapamycin complex 1 (TORC1) controls cell growth in response to nutrient availability and growth factors. TORC1 signaling is hyperactive in cancer, and regulators of TORC1 signaling may represent therapeutic targets for human diseases. To identify novel regulators of TORC1 signaling, we performed a genome-scale RNA interference screen on microarrays of Drosophila melanogaster cells expressing human RPS6, a TORC1 effector whose phosphorylated form we detected by immunofluorescence. Our screen revealed that the TORC1-S6K-RPS6 signaling axis is regulated by many subcellular components, including the Class I vesicle coat (COPI), the spliceosome, the proteasome, the nuclear pore, and the translation initiation machinery. Using additional RNAi reagents, we confirmed 70 novel genes as significant on-target regulators of RPS6 phosphorylation, and we characterized them with extensive secondary assays probing various arms of the TORC1 pathways, identifying functional relationships among those genes. We conclude that cell-based microarrays are a useful platform for genome-scale and secondary screening in Drosophila, revealing regulators that may represent drug targets for cancers and other diseases of deregulated TORC1 signaling.
PubMed ID
PubMed Central ID
PMC3044857 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genome Res.
    Title
    Genome Research
    Publication Year
    1995-
    ISBN/ISSN
    1088-9051
    Data From Reference