![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
RESEARCH PAPER
Division of Molecular Biology of the Cell II, German Cancer Research Center, D-69120 Heidelberg, Germany
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 Ser 44 (S44) and hyperphosphorylation of Ser 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 for mTOR-signaling pathways and elucidate the molecular mechanism underlying mTOR-dependent regulation of rRNA synthesis.
[Keywords: RNA polymerase I; TIF-IA; mTOR; transcription; phosphorylation; PP2A]
Received September 16, 2003; revised version accepted January 16, 2004.
1 These authors conributed equally to this work.
E-MAIL I.Grummt{at}DKFZ-Heidelberg.de; FAX 0049-6221-423404.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Bierhoff, M. Dundr, A. A. Michels, and I. Grummt Phosphorylation by Casein Kinase 2 Facilitates rRNA Gene Transcription by Promoting Dissociation of TIF-IA from Elongating RNA Polymerase I Mol. Cell. Biol., August 15, 2008; 28(16): 4988 - 4998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Grewal, J. R. Evans, and B. A. Edgar Drosophila TIF-IA is required for ribosome synthesis and cell growth and is regulated by the TOR pathway J. Cell Biol., December 17, 2007; 179(6): 1105 - 1113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mieulet, M. Roceri, C. Espeillac, A. Sotiropoulos, M. Ohanna, V. Oorschot, J. Klumperman, M. Sandri, and M. Pende S6 kinase inactivation impairs growth and translational target phosphorylation in muscle cells maintaining proper regulation of protein turnover Am J Physiol Cell Physiol, August 1, 2007; 293(2): C712 - C722. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Dasgupta, R. O. Sprouse, S. French, P. Aprikian, R. Hontz, S. A. Juedes, J. S. Smith, A. L. Beyer, and D. T. Auble Regulation of rRNA Synthesis by TATA-Binding Protein-Associated Factor Mot1 Mol. Cell. Biol., April 15, 2007; 27(8): 2886 - 2896. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Holzel, T. Grimm, M. Rohrmoser, A. Malamoussi, T. Harasim, A. Gruber-Eber, E. Kremmer, and D. Eick The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing Nucleic Acids Res., February 16, 2007; 35(3): 789 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bogoyevitch and B. Kobe Uses for JNK: the Many and Varied Substrates of the c-Jun N-Terminal Kinases Microbiol. Mol. Biol. Rev., December 1, 2006; 70(4): 1061 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Lin, S. Navarro, S. Reddy, and L. Comai CK2-mediated stimulation of Pol I transcription by stabilization of UBF-SL1 interaction Nucleic Acids Res., October 18, 2006; 34(17): 4752 - 4766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang and C. G. Proud The mTOR Pathway in the Control of Protein Synthesis. Physiology, October 1, 2006; 21: 362 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Michels and N. Hernandez Does Pol I talk to Pol II? Coordination of RNA polymerases in ribosome biogenesis Genes & Dev., August 1, 2006; 20(15): 1982 - 1985. [Full Text] [PDF]
|
|
|
|
|
|
A. Laferte, E. Favry, A. Sentenac, M. Riva, C. Carles, and S. Chedin The transcriptional activity of RNA polymerase I is a key determinant for the level of all ribosome components Genes & Dev., August 1, 2006; 20(15): 2030 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Oakes, I. Siddiqi, S. L. French, L. Vu, M. Sato, J. P. Aris, A. L. Beyer, and M. Nomura Role of Histone Deacetylase Rpd3 in Regulating rRNA Gene Transcription and Nucleolar Structure in Yeast Mol. Cell. Biol., May 15, 2006; 26(10): 3889 - 3901. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Anand and P. A. Gruppuso Rapamycin Inhibits Liver Growth during Refeeding in Rats via Control of Ribosomal Protein Translation but Not Cap-Dependent Translation Initiation J. Nutr., January 1, 2006; 136(1): 27 - 33. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zhang, L. Comai, and D. L. Johnson PTEN Represses RNA Polymerase I Transcription by Disrupting the SL1 Complex Mol. Cell. Biol., August 15, 2005; 25(16): 6899 - 6911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mayer, H. Bierhoff, and I. Grummt The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis Genes & Dev., April 15, 2005; 19(8): 933 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Inoki, H. Ouyang, Y. Li, and K.-L. Guan Signaling by Target of Rapamycin Proteins in Cell Growth Control Microbiol. Mol. Biol. Rev., March 1, 2005; 69(1): 79 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Schneider and M. Nomura RNA polymerase I remains intact without subunit exchange through multiple rounds of transcription in Saccharomyces cerevisiae PNAS, October 19, 2004; 101(42): 15112 - 15117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Jorgensen, I. Rupes, J. R. Sharom, L. Schneper, J. R. Broach, and M. Tyers A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size Genes & Dev., October 15, 2004; 18(20): 2491 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hay and N. Sonenberg Upstream and downstream of mTOR Genes & Dev., August 15, 2004; 18(16): 1926 - 1945. [Abstract] [Full Text] [PDF]
|
|
