Requirement of the mTOR kinase for the regulation of Maf1 phosphorylation and control of RNA polymerase III-dependent transcription in cancer cells
What this study shows
The RNA polymerase III half of the same output. Three hours of the mTOR active-site inhibitor WYE-125132 (0.5 uM) cut pre-tRNA-Leu by 53 to 80 percent depending on the line and also lowered pre-tRNA-Tyr. Phosphoproteomics identified Ser75 of Maf1, the repressor of Pol III, as almost completely dephosphorylated after mTOR inhibition. Dephosphorylated Maf1 accumulated in the nucleus and occupied Pol III genes more, while Pol III and Brf1 binding fell. Depleting Maf1 raised basal pre-tRNA and made tRNA synthesis insensitive to mTOR inhibitors, and Maf1 mutants that cannot be phosphorylated blunted the roughly threefold rise in pre-tRNA when amino acids were added back to starved cells. siRNA against mTOR and raptor lowered pre-tRNAs while rictor siRNA had little effect, which points at mTORC1. Boundary: direct phosphorylation of Maf1 by mTOR was NOT detected (reported as data not shown, and the authors themselves caution against reading that negative result too firmly; a rapamycin-resistant S6K1 partly protected Maf1, so S6K1 or another kinase may sit in between). CCI-779 gave a weaker effect than WYE-125132. The 5S rRNA result comes from the Maf1 mutants in supplementary data, not from drug treatment. Cancer cell lines and acute pharmacology; no animal or human data.
At a glance
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| Evidence type | M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cancer lines MG63 (osteosarcoma) and MDA-MB-361 (breast) plus HEK293; U87MG, HCT116, HT29 in supplementary data; mTOR active-site inhibitor WYE-125132 and the rapalog CCI-779; SILAC phosphoproteomics, siRNA, ChIP) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is. |
| Study type | 5 - Mechanistic / In Vitro |
| Model system | Human cancer lines MG63 (osteosarcoma) and MDA-MB-361 (breast) plus HEK293; U87MG, HCT116, HT29 in supplementary data; mTOR active-site inhibitor WYE-125132 and the rapalog CCI-779; SILAC phosphoproteomics, siRNA, ChIP |
| Journal | Journal of Biological Chemistry |
| Year | 2010 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1074/jbc.M109.071639 · PMID 20233713 · Free full text (PMC2865278) |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Pathway relations
Supports
mTORC1 activates Ribosome biogenesisStrongest evidence: M (Molecular — cells, biochemistry, structure) · emerging, few independent studies · Status: Proposed
plausible in people, not shown directly
Both polymerase branches are in the corpus as of 7 November 2026, and both are indirect: neither paper could show mTOR phosphorylating its target. MAY2004 writes that mTOR activates TIF-IA directly or indirectly and reports that…
People in the Atlas
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First author of the 2010 Journal of Biological Chemistry study on mTOR, Maf1 and RNA polymerase III transcription.
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Last author of the 2010 Journal of Biological Chemistry study on mTOR, Maf1 and RNA polymerase III transcription.
More: 5 other authors
No profile yet: Wu J, Shakey Q, Toral-Barza L, Shi C, Follettie M
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Topics
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