Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling (original) (raw)
- Thomas Radimerski1,
- Jacques Montagne1,
- Maja Hemmings-Mieszczak2, and
- George Thomas1,3
- 1Friedrich Miescher Institute for Biomedical Research, CH-4058, Basel, Switzerland; 2Novartis Pharma AG, CH-4056 Basel, Switzerland
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.
Footnotes
↵3 Corresponding author.
E-MAIL gthomas{at}fmi.ch; FAX 41-61-697-3976.
Supplemental material is available at http://www.genesdev.org.
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.239102.
- Received June 20, 2002.
- Accepted August 23, 2002.
Cold Spring Harbor Laboratory Press