Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling
Abstract
Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in one of two tumor suppressor genes, TSC1 andTSC2. 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.
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Footnotes
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↵3 Corresponding author.
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E-MAIL gthomas{at}fmi.ch; FAX 41-61-697-3976.
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Supplemental material is available at http://www.genesdev.org.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.239102.
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- Received June 20, 2002.
- Accepted August 23, 2002.
- Cold Spring Harbor Laboratory Press
