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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Genes Dev 2008, PMID: 18519641

Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK.

Dan, Han C; Cooper, Matthew J; Cogswell, Patricia C; Duncan, Joseph A; Ting, Jenny P-Y; Baldwin, Albert S

While NF-kappaB is considered to play key roles in the development and progression of many cancers, the mechanisms whereby this transcription factor is activated in cancer are poorly understood. A key oncoprotein in a variety of cancers is the serine-threonine kinase Akt, which can be activated by mutations in PI3K, by loss of expression/activity of PTEN, or through signaling induced by growth factors and their receptors. A key effector of Akt-induced signaling is the regulatory protein mTOR (mammalian target of rapamycin). We show here that mTOR downstream from Akt controls NF-kappaB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK. The mTOR-associated protein Raptor is required for the ability of Akt to induce NF-kappaB activity. Correspondingly, the mTOR inhibitor rapamycin is shown to suppress IKK activity in PTEN-deficient prostate cancer cells through a mechanism that may involve dissociation of Raptor from mTOR. The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin.

Diseases/Pathways annotated by Medline MESH: Prostatic Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

NF-{kappa}B → Akt: " Akt dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK "

Raptor — Akt: " Akt dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK "

Raptor — NF-{kappa}B: " Akt dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK "

mTOR — Akt: " Akt dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK "

mTOR — NF-{kappa}B: " Akt dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK "

mTOR — NF-kappaB: " We show here that mTOR downstream from Akt controls NF-kappaB activity in PTEN-null/inactive prostate cancer cells via interaction with and stimulation of IKK "

NF-kappaB ⊣ Raptor: " The mTOR associated protein Raptor is required for the ability of Akt to induce NF-kappaB activity "

NF-kappaB → Akt: " The mTOR associated protein Raptor is required for the ability of Akt to induce NF-kappaB activity "

Manually curated Databases

  • IRef Innatedb Interaction: CHUK — MTOR (unknown, -)
In total, 1 gene pairs are associated to this article in curated databases