This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pestov, D. G.
Right arrow Articles by Lau, L. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pestov, D. G.
Right arrow Articles by Lau, L. F.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2001, p. 4246-4255, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4246-4255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Evidence of p53-Dependent Cross-Talk between Ribosome Biogenesis and the Cell Cycle: Effects of Nucleolar Protein Bop1 on G1/S Transition

Dimitri G. Pestov, Zaklina Strezoska, and Lester F. Lau*

Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, Chicago, Illinois 60607-7170

Received 12 February 2001/Returned for modification 22 March 2001/Accepted 2 April 2001

Bop1 is a novel nucleolar protein involved in rRNA processing and ribosome assembly. We have previously shown that expression of Bop1Delta , an amino-terminally truncated Bop1 that acts as a dominant negative mutant in mouse cells, results in inhibition of 28S and 5.8S rRNA formation and deficiency of newly synthesized 60S ribosomal subunits (Z. Strezoska, D. G. Pestov, and L. F. Lau, Mol. Cell. Biol. 20:5516-5528, 2000). Perturbation of Bop1 activities by Bop1Delta also induces a powerful yet reversible cell cycle arrest in 3T3 fibroblasts. In the present study, we show that asynchronously growing cells are arrested by Bop1Delta in a highly concerted fashion in the G1 phase. Kinase activities of the G1-specific Cdk2 and Cdk4 complexes were downregulated in cells expressing Bop1Delta , whereas levels of the Cdk inhibitors p21 and p27 were concomitantly increased. The cells also displayed lack of hyperphosphorylation of retinoblastoma protein (pRb) and decreased expression of cyclin A, indicating their inability to progress through the restriction point. Inactivation of functional p53 abrogated this Bop1Delta -induced cell cycle arrest but did not restore normal rRNA processing. These findings show that deficiencies in ribosome synthesis can be uncoupled from cell cycle arrest and reveal a new role for the p53 pathway as a mediator of the signaling link between ribosome biogenesis and the cell cycle. We propose that aberrant rRNA processing and/or ribosome biogenesis may cause "nucleolar stress," leading to cell cycle arrest in a p53-dependent manner.

* Corresponding author. Mailing address: Department of Molecular Genetics, University of Illinois at Chicago College of Medicine, 900 S. Ashland Avenue, Chicago, IL 60607-7170. Phone: (312) 996-6978. Fax: (312) 996-7034. E-mail: lflau{at}uic.edu.

Molecular and Cellular Biology, July 2001, p. 4246-4255, Vol. 21, No. 13
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.13.4246-4255.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ge, J., Rudnick, D. A., He, J., Crimmins, D. L., Ladenson, J. H., Bessler, M., Mason, P. J. (2010). Dyskerin Ablation in Mouse Liver Inhibits rRNA Processing and Cell Division. Mol. Cell. Biol. 30: 413-422 [Abstract] [Full Text]  
  • Moore, J. B. IV, Farrar, J. E., Arceci, R. J., Liu, J. M., Ellis, S. R. (2010). Distinct ribosome maturation defects in yeast models of Diamond-Blackfan anemia and Shwachman-Diamond syndrome. haematol 95: 57-64 [Abstract] [Full Text]  
  • Barkic, M., Crnomarkovic, S., Grabusic, K., Bogetic, I., Panic, L., Tamarut, S., Cokaric, M., Jeric, I., Vidak, S., Volarevic, S. (2009). The p53 Tumor Suppressor Causes Congenital Malformations in Rpl24-Deficient Mice and Promotes Their Survival. Mol. Cell. Biol. 29: 2489-2504 [Abstract] [Full Text]  
  • Pederson, T., Tsai, R. Y.L. (2009). In search of nonribosomal nucleolar protein function and regulation. JCB 184: 771-776 [Abstract] [Full Text]  
  • Shen, J., Cowen, L. E., Griffin, A. M., Chan, L., Kohler, J. R. (2008). The Candida albicans pescadillo homolog is required for normal hypha-to-yeast morphogenesis and yeast proliferation. Proc. Natl. Acad. Sci. USA 105: 20918-20923 [Abstract] [Full Text]  
  • Danilova, N., Sakamoto, K. M., Lin, S. (2008). Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family. Blood 112: 5228-5237 [Abstract] [Full Text]  
  • Sihn, C.-R., Lee, Y.-S., Jeong, J.-S., Park, K., Kim, S. H. (2008). CANu1, a novel nucleolar protein, accumulated on centromere in response to DNA damage. GENES CELLS 13: 787-796 [Abstract] [Full Text]  
  • Dai, M.-S., Sun, X.-X., Lu, H. (2008). Aberrant Expression of Nucleostemin Activates p53 and Induces Cell Cycle Arrest via Inhibition of MDM2. Mol. Cell. Biol. 28: 4365-4376 [Abstract] [Full Text]  
  • Castro, M. E., Leal, J. F.M., Lleonart, M. E., Ramon y Cajal, S., Carnero, A. (2008). Loss-of-function genetic screening identifies a cluster of ribosomal proteins regulating p53 function. Carcinogenesis 29: 1343-1350 [Abstract] [Full Text]  
  • Sun, X.-X., Dai, M.-S., Lu, H. (2008). Mycophenolic Acid Activation of p53 Requires Ribosomal Proteins L5 and L11. J. Biol. Chem. 283: 12387-12392 [Abstract] [Full Text]  
  • Choesmel, V., Fribourg, S., Aguissa-Toure, A.-H., Pinaud, N., Legrand, P., Gazda, H. T., Gleizes, P.-E. (2008). Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder. Hum Mol Genet 17: 1253-1263 [Abstract] [Full Text]  
  • D'Arcy, P., Maruwge, W., Ryan, B. A., Brodin, B. (2008). The Oncoprotein SS18-SSX1 Promotes p53 Ubiquitination and Degradation by Enhancing HDM2 Stability. Mol Cancer Res 6: 127-138 [Abstract] [Full Text]  
  • Lapik, Y. R., Misra, J. M., Lau, L. F., Pestov, D. G. (2007). Restricting Conformational Flexibility of the Switch II Region Creates a Dominant-Inhibitory Phenotype in Obg GTPase Nog1. Mol. Cell. Biol. 27: 7735-7744 [Abstract] [Full Text]  
  • Gregory, L. A., Aguissa-Toure, A.-H., Pinaud, N., Legrand, P., Gleizes, P.-E., Fribourg, S. (2007). Molecular basis of Diamond Blackfan anemia: structure and function analysis of RPS19. Nucleic Acids Res 35: 5913-5921 [Abstract] [Full Text]  
  • Griffith, M. E., Mayer, U., Capron, A., Ngo, Q. A., Surendrarao, A., McClinton, R., Jurgens, G., Sundaresan, V. (2007). The TORMOZ Gene Encodes a Nucleolar Protein Required for Regulated Division Planes and Embryo Development in Arabidopsis. Plant Cell 19: 2246-2263 [Abstract] [Full Text]  
  • Ma, H., Pederson, T. (2007). Depletion of the Nucleolar Protein Nucleostemin Causes G1 Cell Cycle Arrest via the p53 Pathway. Mol. Biol. Cell 18: 2630-2635 [Abstract] [Full Text]  
  • Jalal, C., Uhlmann-Schiffler, H., Stahl, H. (2007). Redundant role of DEAD box proteins p68 (Ddx5) and p72/p82 (Ddx17) in ribosome biogenesis and cell proliferation. Nucleic Acids Res 35: 3590-3601 [Abstract] [Full Text]  
  • Rohrmoser, M., Holzel, M., Grimm, T., Malamoussi, A., Harasim, T., Orban, M., Pfisterer, I., Gruber-Eber, A., Kremmer, E., Eick, D. (2007). Interdependence of Pes1, Bop1, and WDR12 Controls Nucleolar Localization and Assembly of the PeBoW Complex Required for Maturation of the 60S Ribosomal Subunit. Mol. Cell. Biol. 27: 3682-3694 [Abstract] [Full Text]  
  • Sun, X.-X., Dai, M.-S., Lu, H. (2007). 5-Fluorouracil Activation of p53 Involves an MDM2-Ribosomal Protein Interaction. J. Biol. Chem. 282: 8052-8059 [Abstract] [Full Text]  
  • Bernstein, K. A., Bleichert, F., Bean, J. M., Cross, F. R., Baserga, S. J. (2007). Ribosome Biogenesis Is Sensed at the Start Cell Cycle Checkpoint. Mol. Biol. Cell 18: 953-964 [Abstract] [Full Text]  
  • Holzel, M., Rohrmoser, M., Orban, M., Homig, C., Harasim, T., Malamoussi, A., Gruber-Eber, A., Heissmeyer, V., Bornkamm, G., Eick, D. (2007). Rapid conditional knock-down-knock-in system for mammalian cells. Nucleic Acids Res 35: e17-e17 [Abstract] [Full Text]  
  • Holzel, M., Grimm, T., Rohrmoser, M., Malamoussi, A., Harasim, T., Gruber-Eber, A., Kremmer, E., Eick, D. (2007). The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing. Nucleic Acids Res 35: 789-800 [Abstract] [Full Text]  
  • Choesmel, V., Bacqueville, D., Rouquette, J., Noaillac-Depeyre, J., Fribourg, S., Cretien, A., Leblanc, T., Tchernia, G., Da Costa, L., Gleizes, P.-E. (2007). Impaired ribosome biogenesis in Diamond-Blackfan anemia. Blood 109: 1275-1283 [Abstract] [Full Text]  
  • Rizos, H., McKenzie, H. A., Ayub, A. L., Woodruff, S., Becker, T. M., Scurr, L. L., Stahl, J., Kefford, R. F. (2006). Physical and Functional Interaction of the p14ARF Tumor Suppressor with Ribosomes. J. Biol. Chem. 281: 38080-38088 [Abstract] [Full Text]  
  • Panic, L., Tamarut, S., Sticker-Jantscheff, M., Barkic, M., Solter, D., Uzelac, M., Grabusic, K., Volarevic, S. (2006). Ribosomal Protein S6 Gene Haploinsufficiency Is Associated with Activation of a p53-Dependent Checkpoint during Gastrulation. Mol. Cell. Biol. 26: 8880-8891 [Abstract] [Full Text]  
  • Yu, L., Castillo, L. P., Mnaimneh, S., Hughes, T. R., Brown, G. W. (2006). A Survey of Essential Gene Function in the Yeast Cell Division Cycle. Mol. Biol. Cell 17: 4736-4747 [Abstract] [Full Text]  
  • Machida, Y. J., Chen, Y., Machida, Y., Malhotra, A., Sarkar, S., Dutta, A. (2006). Targeted Comparative RNA Interference Analysis Reveals Differential Requirement of Genes Essential for Cell Proliferation. Mol. Biol. Cell 17: 4837-4845 [Abstract] [Full Text]  
  • Zhang, F., Hamanaka, R. B., Bobrovnikova-Marjon, E., Gordan, J. D., Dai, M.-S., Lu, H., Simon, M. C., Diehl, J. A. (2006). Ribosomal Stress Couples the Unfolded Protein Response to p53-dependent Cell Cycle Arrest. J. Biol. Chem. 281: 30036-30045 [Abstract] [Full Text]  
  • Dai, M.-S., Shi, D., Jin, Y., Sun, X.-X., Zhang, Y., Grossman, S. R., Lu, H. (2006). Regulation of the MDM2-p53 Pathway by Ribosomal Protein L11 Involves a Post-ubiquitination Mechanism. J. Biol. Chem. 281: 24304-24313 [Abstract] [Full Text]  
  • Liu, J. M., Ellis, S. R. (2006). Ribosomes and marrow failure: coincidental association or molecular paradigm?. Blood 107: 4583-4588 [Abstract] [Full Text]  
  • Azuma, M., Toyama, R., Laver, E., Dawid, I. B. (2006). Perturbation of rRNA Synthesis in the bap28 Mutation Leads to Apoptosis Mediated by p53 in the Zebrafish Central Nervous System. J. Biol. Chem. 281: 13309-13316 [Abstract] [Full Text]  
  • Sulic, S., Panic, L., Barkic, M., Mercep, M., Uzelac, M., Volarevic, S. (2005). Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response. Genes Dev. 19: 3070-3082 [Abstract] [Full Text]  
  • Miles, T. D., Jakovljevic, J., Horsey, E. W., Harnpicharnchai, P., Tang, L., Woolford, J. L. Jr (2005). Ytm1, Nop7, and Erb1 Form a Complex Necessary for Maturation of Yeast 66S Preribosomes. Mol. Cell. Biol. 25: 10419-10432 [Abstract] [Full Text]  
  • Nader, G. A., McLoughlin, T. J., Esser, K. A. (2005). mTOR function in skeletal muscle hypertrophy: increased ribosomal RNA via cell cycle regulators. Am. J. Physiol. Cell Physiol. 289: C1457-C1465 [Abstract] [Full Text]  
  • Bornkamm, G. W., Berens, C., Kuklik-Roos, C., Bechet, J.-M., Laux, G., Bachl, J., Korndoerfer, M., Schlee, M., Holzel, M., Malamoussi, A., Chapman, R. D., Nimmerjahn, F., Mautner, J., Hillen, W., Bujard, H., Feuillard, J. (2005). Stringent doxycycline-dependent control of gene activities using an episomal one-vector system. Nucleic Acids Res 33: e137-e137 [Abstract] [Full Text]  
  • Holzel, M., Rohrmoser, M., Schlee, M., Grimm, T., Harasim, T., Malamoussi, A., Gruber-Eber, A., Kremmer, E., Hiddemann, W., Bornkamm, G. W., Eick, D. (2005). Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation. JCB 170: 367-378 [Abstract] [Full Text]  
  • Angelier, N., Tramier, M., Louvet, E., Coppey-Moisan, M., Savino, T. M., De Mey, J. R., Hernandez-Verdun, D. (2005). Tracking the Interactions of rRNA Processing Proteins during Nucleolar Assembly in Living Cells. Mol. Biol. Cell 16: 2862-2871 [Abstract] [Full Text]  
  • Fang, F., Hoskins, J., Butler, J. S. (2004). 5-Fluorouracil Enhances Exosome-Dependent Accumulation of Polyadenylated rRNAs. Mol. Cell. Biol. 24: 10766-10776 [Abstract] [Full Text]  
  • Trere, D., Ceccarelli, C., Montanaro, L., Tosti, E., Derenzini, M. (2004). Nucleolar Size and Activity Are Related to pRb and p53 Status in Human Breast Cancer. J. Histochem. Cytochem. 52: 1601-1607 [Abstract] [Full Text]  
  • Bernstein, K. A., Baserga, S. J. (2004). The Small Subunit Processome Is Required for Cell Cycle Progression at G1. Mol. Biol. Cell 15: 5038-5046 [Abstract] [Full Text]  
  • Dai, M.-S., Lu, H. (2004). Inhibition of MDM2-mediated p53 Ubiquitination and Degradation by Ribosomal Protein L5. J. Biol. Chem. 279: 44475-44482 [Abstract] [Full Text]  
  • Rudra, D., Warner, J. R. (2004). What better measure than ribosome synthesis?. Genes Dev. 18: 2431-2436 [Full Text]  
  • Jorgensen, P., Rupes, I., Sharom, J. R., Schneper, L., Broach, J. R., Tyers, M. (2004). A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size. Genes Dev. 18: 2491-2505 [Abstract] [Full Text]  
  • Dai, M.-S., Zeng, S. X., Jin, Y., Sun, X.-X., David, L., Lu, H. (2004). Ribosomal Protein L23 Activates p53 by Inhibiting MDM2 Function in Response to Ribosomal Perturbation but Not to Translation Inhibition. Mol. Cell. Biol. 24: 7654-7668 [Abstract] [Full Text]  
  • Jin, A., Itahana, K., O'Keefe, K., Zhang, Y. (2004). Inhibition of HDM2 and Activation of p53 by Ribosomal Protein L23. Mol. Cell. Biol. 24: 7669-7680 [Abstract] [Full Text]  
  • ROSADO, I. V., DE LA CRUZ, J. (2004). Npa1p is an essential trans-acting factor required for an early step in the assembly of 60S ribosomal subunits in Saccharomyces cerevisiae. RNA 10: 1073-1083 [Abstract] [Full Text]  
  • Henning, D., So, R. B., Jin, R., Lau, L. F., Valdez, B. C. (2003). Silencing of RNA Helicase II/Gu{alpha} Inhibits Mammalian Ribosomal RNA Production. J. Biol. Chem. 278: 52307-52314 [Abstract] [Full Text]  
  • Schlosser, I., Holzel, M., Murnseer, M., Burtscher, H., Weidle, U. H., Eick, D. (2003). A role for c-Myc in the regulation of ribosomal RNA processing. Nucleic Acids Res 31: 6148-6156 [Abstract] [Full Text]  
  • Lerch-Gaggl, A., Haque, J., Li, J., Ning, G., Traktman, P., Duncan, S. A. (2002). Pescadillo Is Essential for Nucleolar Assembly, Ribosome Biogenesis, and Mammalian Cell Proliferation. J. Biol. Chem. 277: 45347-45355 [Abstract] [Full Text]  
  • Kim, M., Ahn, J.-W., Song, K., Paek, K.-H., Pai, H.-S. (2002). Forkhead-associated Domains of the Tobacco NtFHA1 Transcription Activator and the Yeast Fhl1 Forkhead Transcription Factor Are Functionally Conserved. J. Biol. Chem. 277: 38781-38790 [Abstract] [Full Text]  
  • Strezoska, Z., Pestov, D. G., Lau, L. F. (2002). Functional Inactivation of the Mouse Nucleolar Protein Bop1 Inhibits Multiple Steps in Pre-rRNA Processing and Blocks Cell Cycle Progression. J. Biol. Chem. 277: 29617-29625 [Abstract] [Full Text]  
  • KUROSAWA, A., MIWA, H., HIROSE, M., TSUNE, I., NAGAHARA, A., SATO, N. (2002). Inhibition of cell proliferation and induction of apoptosis by Helicobacter pylori through increased phosphorylated p53, p21 and Bax expression in endothelial cells. J Med Microbiol 51: 385-391 [Abstract] [Full Text]  
  • Adilakshmi, T., Laine, R. O. (2002). Ribosomal Protein S25 mRNA Partners with MTF-1 and La to Provide a p53-mediated Mechanism for Survival or Death. J. Biol. Chem. 277: 4147-4151 [Abstract] [Full Text]  
  • Pestov, D. G., Stockelman, M. G., Strezoska, Z., Lau, L. F. (2001). ERB1, the yeast homolog of mammalian Bop1, is an essential gene required for maturation of the 25S and 5.8S ribosomal RNAs. Nucleic Acids Res 29: 3621-3630 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»