Proc Natl Acad Sci U S A 2009,
PMID: 20080789
Ramanathan, Arvind; Schreiber, Stuart L
mTOR is a central regulator of cellular growth and metabolism. Using metabolic profiling and numerous small-molecule probes, we investigated whether mTOR affects immediate control over cellular metabolism by posttranslational mechanisms. Inhibiting the FKBP12/rapamycin-sensitive subset of mTOR functions in leukemic cells enhanced aerobic glycolysis and decreased uncoupled mitochondrial respiration within 25 min. mTOR is in a complex with the mitochondrial outer-membrane protein Bcl-xl and VDAC1. Bcl-xl, but not VDAC1, is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR. Inhibition of mTOR not only enhances aerobic glycolysis, but also induces a state of increased dependence on aerobic glycolysis in leukemic cells, as shown by the synergy between the glycolytic inhibitor 2-deoxyglucose and rapamycin in decreasing cell viability.
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Text Mining Data
Bcl-xl → VDAC1: " Bcl-xl, but not
VDAC1 , is a kinase substrate for mTOR in vitro, and mTOR
regulates the association of
Bcl-xl with mTOR "
Bcl-xl → mTOR: " Bcl-xl, but not VDAC1, is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR "
VDAC1 — mTOR: " Bcl-xl, but not VDAC1 , is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR "
Manually curated Databases
-
IRef Dip Interaction:
VDAC1
—
BCL2L1
(physical association, anti bait coimmunoprecipitation)
-
IRef Dip Interaction:
Complex of BCL2L1-VDAC1-MTOR
(anti bait coimmunoprecipitation)
-
IRef Dip Interaction:
BCL2L1
—
MTOR
(direct interaction, protein kinase assay)
-
IRef Dip Interaction:
BCL2L1
—
MTOR
(direct interaction, anti bait coimmunoprecipitation)
In total, 3 gene pairs are associated to this article in curated databases