TOR signaling regulates ribosome and tRNA synthesis via LAMMER/Clk and GSK-3 family kinases.

Publication Type:



Molecular cell, Volume 45, Issue 6, p.836-43 (2012)


Glycogen Synthase Kinase 3digestive disease, digestive deseases Phosphorylationdigestive disease, digestive deseases Protein-Serine-Threonine Kinasesdigestive disease, digestive deseases Ribosomesdigestive disease, digestive deseases RNA Polymerase IIIdigestive disease, digestive deseases RNA, Transferdigestive disease, digestive deseases Saccharomyces cerevisiaedigestive disease, digestive deseases Saccharomyces cerevisiae Proteinsdigestive disease, digestive deseases Signal Transductiondigestive disease, digestive deseases Sirolimusdigestive disease, digestive deseases Transcription Factors


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.