Genes Dev 2004,
PMID: 15004009
Mayer, Christine; Zhao, Jian; Yuan, Xuejun; Grummt, Ingrid
In cycling cells, transcription of ribosomal RNA genes by RNA polymerase I (Pol I) is tightly coordinated with cell growth. Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability. Inhibition of mTOR signaling by rapamycin inactivates TIF-IA and impairs transcription-initiation complex formation. Moreover, rapamycin treatment leads to translocation of TIF-IA into the cytoplasm. Rapamycin-mediated inactivation of TIF-IA is caused by hypophosphorylation of Se 44 (S44) and hyperphosphorylation of Se 199 (S199). Phosphorylation at these sites affects TIF-IA activity in opposite ways, for example, phosphorylation of S44 activates and S199 inactivates TIF-IA. The results identify a new target formTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of RNA synthesis.
Document information provided by NCBI PubMed
Text Mining Data
TIF-IA → mTOR: "
mTOR dependent activation of the transcription factor
TIF-IA links rRNA synthesis to nutrient availability
"
Pol I → mammalian target of rapamycin (mTOR): "
Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA, a regulatory factor that senses nutrient and growth-factor availability
"
mammalian target of rapamycin (mTOR) — TIF-IA: "
Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA , a regulatory factor that senses nutrient and growth-factor availability
"
Pol I — TIF-IA: "
Here, we show that the mammalian target of rapamycin (mTOR) regulates Pol I transcription by modulating the activity of TIF-IA , a regulatory factor that senses nutrient and growth-factor availability
"
Manually curated Databases
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IRef Biogrid Interaction:
RRN3
—
CDK2
(direct interaction, pull down)
-
IRef Biogrid Interaction:
PPP2R2A
—
RRN3
(direct interaction, pull down)
-
IRef Biogrid Interaction:
CCNE1
—
CDK2
(direct interaction, pull down)
-
IRef Biogrid Interaction:
CCNE1
—
RRN3
(direct interaction, pull down)
-
IRef Hprd Interaction:
RRN3
—
POLR1B
(in vitro)
-
IRef Hprd Interaction:
RRN3
—
POLR1B
(in vivo)
-
IRef Hprd Interaction:
EIF3L
—
RRN3
(in vivo)
-
IRef Hprd Interaction:
EIF3L
—
RRN3
(in vitro)
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
CDK2/Cyclin E1 complex (CDK2-CCNE1)
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
TIFIA (RRN3)
(modification, activates)
Evidence: mutant phenotype, assay
-
NCI Pathway Database mTOR signaling pathway:
CDK2/Cyclin E1 complex (CDK2-CCNE1)
→
TIFIA (RRN3)
(modification, activates)
Evidence: mutant phenotype, assay
In total, 18 gene pairs are associated to this article in curated databases