Abstract

Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in one of two tumor suppressor genes, TSC1 and TSC2 . Here, we show that absence of Drosophila Tsc1/2 leads to constitutive dS6K activation and inhibition of dPKB, the latter effect being relieved by loss of dS6K. In contrast, the dPTEN tumor suppressor, a negative effector of PI3K, has little effect on dS6K, but negatively regulates dPKB. More importantly, we demonstrate that reducing dS6K signaling rescues early larval lethality associated with loss of dTsc1/2 function, arguing that the S6K pathway is a promising target for the treatment of TSC.

Keywords

TSC1BiologySuppressorTSC2EffectorLoss functionTuberous sclerosisTumor suppressor geneP70-S6 Kinase 1Cancer researchGeneDrosophila (subgenus)Function (biology)Genetic screenGeneticsCell biologySignal transductionPI3K/AKT/mTOR pathwayPhenotypeCarcinogenesis

MeSH Terms

AnimalsCell DivisionDown-RegulationDrosophila melanogasterEnzyme ActivationEyeGenesInsectGenesLethalGenesTumor SuppressorMutationPTEN PhosphohydrolasePhosphatidylinositol 3-KinasesPhosphatidylinositol PhosphatesPhosphoric Monoester HydrolasesProtein Serine-Threonine KinasesProtein-Tyrosine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktRNADouble-StrandedRibosomal Protein S6 KinasesSignal TransductionTuberous SclerosisTumor Suppressor ProteinsWingsAnimal

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Publication Info

Year
2002
Type
article
Volume
16
Issue
20
Pages
2627-2632
Citations
181
Access
Closed

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Cite This

Thomas Radimerski, Jacques Montagne, Maja Hemmings-Mieszczak et al. (2002). Lethality of <i>Drosophila</i> lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes & Development , 16 (20) , 2627-2632. https://doi.org/10.1101/gad.239102

Identifiers

DOI
10.1101/gad.239102
PMID
12381661
PMCID
PMC187466

Data Quality

Data completeness: 86%