Cancer Cell 2006,
Ghosh, Sourav; Tergaonkar, Vinay; Rothlin, Carla V; Correa, Ricardo G; Bottero, Virginie; Bist, Pradeep; Verma, Inder M; Hunter, Tony
The TSC1-TSC2 complex has recently been implicated in cell survival responses. We observed that NF-kappaB signaling is attenuated in TSC1- and TSC2-deficient MEFs concomitant with reduced survival following DNA damage or TNFalpha stimulation. Reconstitution of TSC2 expression in TSC2(-/-) MEFs rescued survival in an NF-kappaB activity-dependent manner. Furthermore, in TSC2(-/-) MEFs, the rapamycin-mediated inhibition of deregulated mTOR activity restored NF-kappaB activation and survival. This rapamycin-mediated effect was reversed by inhibition of NF-kappaB transcriptional activation or by inhibition of ERK1/2 MAP kinase or PI-3K pathways, which lie on signaling cascades that lead to NF-kappaB activation. These results provide evidence for a crosstalk between the TSC/Rheb/mTOR pathway and the NF-kappaB induction pathways and indicate that NF-kappaB functions as an important survival factor that regulates TSC2-dependent cell survival.
Diseases/Pathways annotated by Medline MESH:
MAP Kinase Signaling System
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Text Mining Data
NF-kappaB ⊣ mTOR: " Furthermore, in TSC2 ( -/- ) MEFs, the rapamycin mediated inhibition of deregulated mTOR
activity restored NF-kappaB
activation and survival "
Manually curated Databases
No curated data.