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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 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.

SUBMITTER: Radimerski T

PROVIDER: S-EPMC187466 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling.

Radimerski Thomas T Montagne Jacques J Hemmings-Mieszczak Maja M Thomas George G

Genes & development 20021001 20

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 l ...[more]

PMID: 12381661

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