TY - JOUR
T1 - Ribosomal protein S6 kinase activity controls the ribosome biogenesis transcriptional program
AU - Chauvin, C.
AU - Koka, V.
AU - Nouschi, A.
AU - Mieulet, V.
AU - Hoareau-Aveilla, C.
AU - Dreazen, A.
AU - Cagnard, N.
AU - Carpentier, W.
AU - Kiss, T.
AU - Meyuhas, O.
AU - Pende, M.
PY - 2014/1/23
Y1 - 2014/1/23
N2 - S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2-/- cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.
AB - S6 kinases (S6Ks) are mechanistic target of rapamycin substrates that participate in cell growth control. S6Ks phosphorylate ribosomal protein S6 (rpS6) and additional proteins involved in the translational machinery, although the functional roles of these modifications remain elusive. Here we analyze the S6K-dependent transcriptional and translational regulation of gene expression by comparing whole-genome microarray of total and polysomal mouse liver RNA after feeding. We show that tissue lacking S6Ks 1 and 2 (S6K1 and S6K2), displays a defect in the ribosome biogenesis (RiBi) transcriptional program after feeding. Over 75% of RiBi factors are controlled by S6K, including Nop56, Nop14, Gar1, Rrp9, Rrp15, Rrp12 and Pwp2 nucleolar proteins. Importantly, the reduced activity of RiBi transcriptional promoters in S6K1;S6K2-/- cells is also observed in rpS6 knock-in mutants that cannot be phosphorylated. As ribosomal protein synthesis is not affected by these mutations, our data reveal a distinct and specific aspect of RiBi under the control of rpS6 kinase activity, that is, the RiBi transcriptional program.
KW - mTOR
KW - Ribosome biogenesis
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=84896629473&partnerID=8YFLogxK
U2 - 10.1038/onc.2012.606
DO - 10.1038/onc.2012.606
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C2 - 23318442
AN - SCOPUS:84896629473
SN - 0950-9232
VL - 33
SP - 474
EP - 483
JO - Oncogene
JF - Oncogene
IS - 4
ER -