Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling
AUTOR(ES)
Radimerski, Thomas
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=187466Documentos Relacionados
- Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3
- Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex
- The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila
- TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth
- Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2