TOR Signaling Regulates Ribosome and tRNA Synthesis via LAMMER/Clk and GSK-3 Family Kinases

Jaehoon Lee, Robyn D. Moir, Kerri B. McIntosh, Ian M.W. Willis

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Target of rapamycin (TOR)-dependent signaling and the control of cell growth is deregulated in many cancers. However, the signaling molecules downstream of TOR that coordinately regulate the synthesis of ribosomes and tRNAs are not well defined. Here, we show in yeast that conserved kinases of the LAMMER/Cdc-like and GSK-3 families function downstream of TOR complex 1 to repress ribosome and tRNA synthesis in response to nutrient limitation and other types of cellular stress. As a part of this response, we found that the LAMMER kinase Kns1 is differentially expressed and hyperphosphorylated and accumulates in the nucleus after rapamycin treatment, whereupon it primes the phosphorylation of the RNA polymerase III subunit Rpc53 by a specific GSK-3 family member, Mck1. In cooperation with another polymerase subunit, Rpc11, this phosphorylation of Rpc53 modifies the function of the enzyme and together with dephosphorylation of the Maf1 repressor inhibits the growth-promoting activity of RNA polymerase III transcription.

Original languageEnglish (US)
Pages (from-to)836-843
Number of pages8
JournalMolecular Cell
Volume45
Issue number6
DOIs
Publication statusPublished - Mar 30 2012

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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