Functional ribosome biogenesis is a prerequisite for p53 destabilization: Impact of chemotherapy on nucleolar functions and RNA metabolism

Biological Chemistry

Volumn 394, Issue 9, 2013, Pages 1133-1143

  Burger, Kaspar ^a   Eick, Dirk ^a  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

Author keywords

Chemotherapy; Kinase inhibitor; Ribosome biogenesis; TRNA processing; Tumor suppressor p53

Indexed keywords

5,6 DICHLOROBENZIMIDAZOLE RIBOSIDE; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; ANTINEOPLASTIC AGENT; CHECKPOINT KINASE 1; CX 5461; CYCLIN DEPENDENT KINASE; DACTINOMYCIN; DAUNORUBICIN; DOXORUBICIN; EXONUCLEASE; FLAVOPIRIDOL; FLUOROURACIL; MITOMYCIN; OLOMOUCINE; PROTEIN P53; QUARFLOXIN; RIBOSOME RNA; RNA 18S; RNA 28S; RNA 5.8S; ROSCOVITINE; UNCLASSIFIED DRUG;

ACROCENTRIC CHROMOSOME; ACUTE LYMPHOBLASTIC LEUKEMIA; APOPTOSIS; AUTOPHAGY; BIOGENESIS; CANCER CELL; CANCER CHEMOTHERAPY; CANCER SUSCEPTIBILITY; CANCER THERAPY; CELL CYCLE ARREST; CELL ENERGY; CELL GROWTH; CELL PROLIFERATION; CELL STRESS; CELLULAR STRESS RESPONSE; CHILDHOOD CANCER; CHRONIC LYMPHATIC LEUKEMIA; DNA DAMAGE; DNA METABOLISM; DNA STRAND BREAKAGE; GENE CONTROL; HUMAN; LYMPHOMA CELL; NONHUMAN; NUCLEOLUS; PHOSPHORYLATION; PRIORITY JOURNAL; REVIEW; RIBOSOME; RNA METABOLISM; SIGNAL TRANSDUCTION; TRANSCRIPTION INITIATION; UPREGULATION;

ANIMALS; CELL NUCLEOLUS; HUMANS; PROTEIN BIOSYNTHESIS; RIBOSOMAL PROTEINS; RIBOSOMES; RNA; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84881532614     PISSN: 14316730     EISSN: 14374315     Source Type: Journal    
DOI: 10.1515/hsz-2013-0153     Document Type: Review

References (121)

1. Andersen, J.S., Lam, Y.W., Leung, A.K., Ong, S.E., Lyon, C.E., Lamond, A.I., and Mann, M. (2005). Nucleolar proteome dynamics. Nature 433, 77 - 83.
2. Andrews, W.J., Panova, T., Normand, C., Gadal, O., Tikhonova, I.G., and Panov, K.I. (2013). Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription. J. Biol. Chem. 288, 4567 - 4582.
3. Bakin, A., Lane, B.G., and Ofengand, J. (1994). Clustering of pseudouridine residues around the peptidyltransferase center of yeast cytoplasmic and mitochondrial ribosomes. Biochemistry 33, 13475 - 13483.
4. Bartek, J. and Lukas, J. (2003). Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3, 421 - 429.
5. Baumas, K., Soudet, J., Caizergues-Ferrer, M., Faubladier, M., Henry, Y., and Mougin, A. (2012). Human RioK3 is a novel component of cytoplasmic pre-40S pre-ribosomal particles. RNA Biol. 9, 162 - 174.
6. Berger, E. (1977). The ribosomes of Drosophila, Normal and defective ribosome biosynthesis in Drosophila cell cultures. Mol. Gen. Genet. 155, 35 - 40.
7. Berry, J.P., Galle, P., Viron, A., Kacerovska, H., and Macieira-Coelho, A. (1983). Preferential nucleolar localization of Cis-DDP in human fibroblasts. Biomed. Pharmacother. 37, 125- 129.
8. Bhat, K.P., Itahana, K., Jin, A., and Zhang, Y. (2004). Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation. EMBO J. 23, 2402 - 2412.
9. Blattner, C., Tobiasch, E., Litfen, M., Rahmsdorf, H.J., and Herrlich, P. (1999). DNA damage induced p53 stabilization: no indication for an involvement of p53 phosphorylation. Oncogene 18, 1723 - 1732.
10. Boisvert, F.M., van Koningsbruggen, S., Navascues, J., and Lamond, A.I. (2007). The multifunctional nucleolus. Nat. Rev. Mol. Cell Biol. 8, 574 - 585.
11. Boon, K., Caron, H.N., van Asperen, R., Valentijn, L., Hermus, M.C., van Sluis, P., Roobeek, I., Weis, I., Voute, P.A., Schwab, M., et al. (2001). N-myc enhances the expression of a large set of genes functioning in ribosome biogenesis and protein synthesis. EMBO J. 20, 1383 - 1393.
12. Boyd, M.T., Vlatkovic, N., and Rubbi, C.P. (2011). The nucleolus directly regulates p53 export and degradation. J. Cell Biol. 194, 689 - 703.
13. Brown, D.D. and Gurdon, J.B. (1964). Absence of ribosomal RNA synthesis in the anucleolate mutant of Xenopus Laevis. Proc. Natl. Acad. Sci. USA 51, 139 - 146.
14. Bunz, F., Hwang, P.M., Torrance, C., Waldman, T., Zhang, Y., Dillehay, L., Williams, J., Lengauer, C., Kinzler, K.W., and Vogelstein, B. (1999). Disruption of p53 in human cancer cells alters the responses to therapeutic agents. J. Clin. Invest. 104, 263 - 269.
15. Burger, K., Muhl, B., Harasim, T., Rohrmoser, M., Malamoussi, A., Orban, M., Kellner, M., Gruber-Eber, A., Kremmer, E., Holzel, M., et al. (2010). Chemotherapeutic drugs inhibit ribosome biogenesis at various levels. J. Biol. Chem. 285, 12416- 12425.
16. Bursac, S., Brdovcak, M.C., Pfannkuchen, M., Orsolic, I., Golomb, L., Zhu, Y., Katz, C., Daftuar, L., Grabusic, K., Vukelic, I., et al. (2012). Mutual protection of ribosomal proteins L5 and L11 from degradation is essential for p53 activation upon ribosomal biogenesis stress. Proc. Natl. Acad. Sci. USA 109, 20467 - 20472.
17. Byrd, J.C., Lin, T.S., Dalton, J.T., Wu, D., Phelps, M.A., Fischer, B., Moran, M., Blum, K.A., Rovin, B., Brooker-McEldowney, M., et al. (2007). Flavopiridol administered using a pharmacologically derived schedule is associated with marked clinical efficacy in refractory, genetically high-risk chronic lymphocytic leukemia. Blood 109, 399 - 404.
18. Bywater, M.J., Poortinga, G., Sanij, E., Hein, N., Peck, A., Cullinane, C., Wall, M., Cluse, L., Drygin, D., Anderes, K., et al. (2012). Inhibition of RNA polymerase I as a therapeutic strategy to promote cancer-specific activation of p53. Cancer Cell 22, 51 - 65.
19. Carson, D.A. and Lois, A. (1995). Cancer progression and p53. Lancet 346, 1009 - 1011.
20. Chan, J.C., Hannan, K.M., Riddell, K., Ng, P.Y., Peck, A., Lee, R.S., Hung, S., Astle, M.V., Bywater, M., Wall, M., et al. (2011). AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in cancer. Sci Signal 4, 56.
21. Chan, P.K., Aldrich, M.B., and Chakrabarty, S. (1988). Assessment of tumor cell sensitivity to mitomycin C by B23 translocation assay. Cancer Lett. 40, 143 - 149.
22. Chan, P.K., Aldrich, M.B., and Yung, B.Y. (1987). Nucleolar protein B23 translocation after doxorubicin treatment in murine tumor cells. Cancer Res 47, 3798 - 3801.
23. Chan, P.K., Qi, Y., Amley, J., and Koller, C.A. (1996). Quantitation of the nucleophosmin/B23-translocation using imaging analysis. Cancer Lett. 100, 191 - 197.
24. Dai, M.S. and Lu, H. (2004). Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5. J. Biol. Chem. 279, 44475 - 44482.
25. Dai, M.S., Zeng, S.X., Jin, Y., Sun, X.X., David, L., and 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.
26. Daskal, Y., Woodard, C., Crooke, S.T., and Busch, H. (1978). Comparative ultrastructural studies of nucleoli of tumor cells treated with adriamycin and the newer anthracyclines, carminomycin and marcellomycin. Cancer Res. 38, 467 - 473.
27. David-Pfeuty, T. (1999). Potent inhibitors of cyclin-dependent kinase 2 induce nuclear accumulation of wild-type p53 and nucleolar fragmentation in human untransformed and tumor-derived cells. Oncogene 18, 7409 - 7422.
28. David-Pfeuty, T., Nouvian-Dooghe, Y., Sirri, V., Roussel, P., and Andez-Verdun, D. (2001). Common and reversible regulation of wild-type p53 function and of ribosomal biogenesis by protein kinases in human cells. Oncogene 20, 5951 - 5963.
29. De Keersmaecker, K., Atak, Z.K., Li, N., Vicente, C., Patchett, S., Girardi, T., Gianfelici, V., Geerdens, E., Clappier, E., Porcu, M., et al. (2013). Exome sequencing identifies mutation in CNOT3 and ribosomal genes RPL5 and RPL10 in T-cell acute lymphoblastic leukemia. Nat. Genet. 45, 186 - 190.
30. Derenzini, M., Trere, D., Pession, A., Govoni, M., Sirri, V., and Chieco, P. (2000). Nucleolar size indicates the rapidity of cell proliferation in cancer tissues. J. Pathol. 191, 181 - 186.
31. Derenzini, M., Trere, D., Pession, A., Montanaro, L., Sirri, V., and Ochs, R.L. (1998). Nucleolar function and size in cancer cells. Am. J. Pathol. 152, 1291 - 1297.
32. Drygin, D., Lin, A., Bliesath, J., Ho, C.B., O'Brien, S.E., Proffitt, C., Omori, M., Haddach, M., Schwaebe, M.K., Siddiqui-Jain, A., et al. (2011). Targeting RNA polymerase I with an oral small molecule CX-5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 71, 1418 - 1430.
33. Drygin, D., Rice, W.G., and Grummt, I. (2010). The RNA polymerase I transcription machinery: An emerging target for the treatment of cancer. Annu. Rev. Pharmacol. Toxicol. 50, 131 - 156.
34. Drygin, D., Siddiqui-Jain, A., O'Brien, S., Schwaebe, M., Lin, A., Bliesath, J., Ho, C.B., Proffitt, C., Trent, K., Whitten, J.P., et al. (2009). Anticancer activity of CX-3543: A direct inhibitor of rRNA biogenesis. Cancer Res. 69, 7653 - 7661.
35. Efeyan, A., Garcia-Cao, I., Herranz, D., Velasco-Miguel, S., and Serrano, M. (2006). Tumour biology: policing of oncogene activity by p53. Nature 443, 159.
36. Eichler, D.C. and Craig, N. (1994). Processing of eukaryotic ribosomal RNA. Prog. Nucleic Acid. Res. Mol. Biol. 49, 197 - 239.
37. Engelman, J.A. (2009). Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat. Rev. Cancer 9, 550 - 562.
38. Falini, B., Bolli, N., Liso, A., Martelli, M.P., Mannucci, R., Pileri, S., and Nicoletti, I. (2009). Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications. Leukemia 23, 1731 - 1743.
39. Fetherston, J., Werner, E., and Patterson, R. (1984). Processing of the exteRNAl transcribed spacer of murine rRNA and site of action of actinomycin D. Nucleic Acids Res. 12, 7187 - 7198.
40. Fritsche, M., Haessler, C., and Brandner, G. (1993). Induction of nuclear accumulation of the tumor-suppressor protein p53 by DNA-damaging agents. Oncogene 8, 307 - 318.
41. Ghobrial, I.M., Gertz, M., Laplant, B., Camoriano, J., Hayman, S., Lacy, M., Chuma, S., Harris, B., Leduc, R., Rourke, M., et al. (2010). Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J. Clin. Oncol. 28, 1408 - 1414.
42. Ghoshal, K. and Jacob, S.T. (1994). Specific inhibition of pre-ribosomal RNA processing in extracts from the lymphosarcoma cells treated with 5-fluorouracil. Cancer Res. 54, 632 - 636.
43. Gilder, A.S., Do, P.M., Carrero, Z.I., Cosman, A.M., Broome, H.J., Velma, V., Martinez, L.A., and Hebert, M.D. (2011). Coilin participates in the suppression of RNA polymerase I in response to cisplatin-induced DNA damage. Mol. Biol. Cell 22, 1070 - 1079.
44. Greenhalgh, D.A. and Parish, J.H. (1990). Effect of 5-fluorouracil combination therapy on RNA processing in human colonic carcinoma cells. Br. J. Cancer 61, 415 - 419.
45. Grimm, T., Holzel, M., Rohrmoser, M., Harasim, T., Malamoussi, A., Gruber-Eber, A., Kremmer, E., and Eick, D. (2006). Dominantnegative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex. Nucleic Acids Res. 34, 3030 - 3043.
46. Grisendi, S., Mecucci, C., Falini, B., and Pandolfi, P.P. (2006). Nucleophosmin and cancer. Nat. Rev. Cancer 6, 493 - 505.
47. Haaf, T. and Ward, D.C. (1996). Inhibition of RNA polymerase II transcription causes chromatin decondensation, loss of nucleolar structure, and dispersion of chromosomal domains. Exp. Cell. Res. 224, 163 - 173.
48. Hadjiolova, K.V., Nicoloso, M., Mazan, S., Hadjiolov, A.A., and Bachellerie, J.P. (1993). AlteRNAtive pre-rRNA processing pathways in human cells and their alteration by cycloheximideinhibition of protein synthesis. Eur. J. Biochem. 212, 211 - 215.
49. Haindl, M., Harasim, T., Eick, D., and Muller, S. (2008). The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing. EMBO Rep. 9, 273 - 279.
50. Hannan, K.M., Sanij, E., Hein, N., Hannan, R.D., and Pearson, R.B. (2011). Signaling to the ribosome in cancer - it is more than just mTORC1. IUBMB Life 63, 79 - 85.
51. Harper, J.W., Elledge, S.J., Keyomarsi, K., Dynlacht, B., Tsai, L.H., Zhang, P., Dobrowolski, S., Bai, C., Connell-Crowley, L., Swindell, E., et al. (1995). Inhibition of cyclin-dependent kinases by p21. Mol. Biol. Cell. 6, 387 - 400.
52. HeRNAndez-Verdun, D., Roussel, P., Thiry, M., Sirri, V., and Lafontaine, D.L. (2010). The nucleolus: structure/function relationship in RNA metabolism Wiley Interdiscip. Rev. RNA 1, 415 - 431.
53. Holzel, M., Burger, K., Muhl, B., Orban, M., Kellner, M., and Eick, D. (2010a). The tumor suppressor p53 connects ribosome biogenesis to cell cycle control: A double-edged sword. Oncotarget 1, 43 - 47.
54. Holzel, M., Grimm, T., Rohrmoser, M., Malamoussi, A., Harasim, T., Gruber-Eber, A., Kremmer, E., and Eick, D. (2007). The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing. Nucleic Acids Res. 35, 789 - 800.
55. Holzel, M., Orban, M., Hochstatter, J., Rohrmoser, M., Harasim, T., Malamoussi, A., Kremmer, E., Langst, G., and Eick, D. (2010b). Defects in 18 S or 28 S rRNA processing activate the p53 pathway. J. Biol. Chem. 285, 6364 - 6370.
56. Holzel, M., Rohrmoser, M., Schlee, M., Grimm, T., Harasim, T., Malamoussi, A., Gruber-Eber, A., Kremmer, E., Hiddemann, W., Bornkamm, G.W., et al. (2005). Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation. J. Cell. Biol. 170, 367 - 378.
57. Hoskins, J. and Butler, J.S. (2008). RNA-based 5-fluorouracil toxicity requires the pseudouridylation activity of Cbf5p. Genetics 179, 323 - 330.
58. Iadevaia, V., Zhang, Z., Jan, E., and Proud, C.G. (2012). mTOR signaling regulates the processing of pre-rRNA in human cells. Nucleic Acids Res. 40, 2527 - 2539.
59. Itahana, K., Bhat, K.P., Jin, A., Itahana, Y., Hawke, D., Kobayashi, R., and Zhang, Y. (2003). Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol. Cell. 12, 1151 - 1164.
60. Jordan, P. and Carmo-Fonseca, M. (1998). Cisplatin inhibits synthesis of ribosomal RNA in vivo. Nucleic Acids Res. 26, 2831 - 2836.
61. Kacerovska, H., Likovsky, Z., and Smetana, K. (1981). Nucleolar silver stained granules in rat Yoshida sarcoma cells after RNA synthesis inhibition. Neoplasma 28, 513 - 516.
62. Kiss, T. (2002). Small nucleolar RNAs: An abundant group of noncoding RNAs with diverse cellular functions. Cell 109, 145 - 148.
63. Kondrashov, N., Pusic, A., Stumpf, C.R., Shimizu, K., Hsieh, A.C., Xue, S., Ishijima, J., Shiroishi, T., and BaRNA, M. (2011). Ribosome-mediated specificity in Hox mRNA translation and vertebrate tissue patterning. Cell 145, 383 - 397.
64. Kuroda, T., Murayama, A., Katagiri, N., Ohta, Y.M., Fujita, E., Masumoto, H., Ema, M., Takahashi, S., Kimura, K., and Yanagisawa, J. (2011). RNA content in the nucleolus alters p53 acetylation via MYBBP1A. EMBO J. 30, 1054 - 1066.
65. Lane, D.P. (1992). Cancer: p53, guardian of the genome. Nature 358, 15-16.
66. Lapik, Y.R., FeRNAndes, C.J., Lau, L.F., and Pestov, D.G. (2004). Physical and functional interaction between Pes1 and Bop1 in mammalian ribosome biogenesis. Mol. Cell. 15, 17 - 29.
67. Leibbrandt, M.E., Wolfgang, G.H., Metz, A.L., Ozobia, A.A., and Haskins, J.R. (1995). Critical subcellular targets of cisplatin and related platinum analogs in rat renal proximal tubule cells. Kidney Int. 48, 761 - 770.
68. Levine, A.J. (1997). p53, the cellular gatekeeper for growth and division. Cell 88, 323 - 331.
69. Likovsky, Z., Peterka, M., and Peterkova, R. (1993). Drug-induced changes of rRNA biosynthesis - A marker of toxic damage to embryonal cell population. Funct. Dev. Morphol. 3, 3 - 9.
70. Lin, T.S., Ruppert, A.S., Johnson, A.J., Fischer, B., Heerema, N.A., Andritsos, L.A., Blum, K.A., Flynn, J.M., Jones, J.A., Hu, W., et al. (2009). Phase II study of flavopiridol in relapsed chronic lymphocytic leukemia demonstrating high response rates in genetically high-risk disease. J. Clin. Oncol. 27, 6012 - 6018.
71. Lindstrom, M.S. (2011). NPM1/B23: A multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem. Res. Int. 2011, 195209.
72. Ljungman, M. (2000). Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress. Neoplasia 2, 208 - 225.
73. Lohrum, M.A., Ludwig, R.L., Kubbutat, M.H., Hanlon, M., and Vousden, K.H. (2003). Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3, 577 - 587.
74. Louvet, E., Junera, H.R., Le Panse, S., and Hernandez-Verdun, D. (2005). Dynamics and compartmentation of the nucleolar processing machinery. Exp. Cell Res. 304, 457 - 470.
75. Matejokova, E. and Smetana, K. (1975). Morphological changes in the nucleoli of peripheral-blood lymphocytes as prognostic criteria in the chemotherapy of malignant tumors. Neoplasma 22, 303 - 312.
76. Merski, J.A., Daskal, I., and Busch, H. (1976). Effects of adriamycin on ultrastructure of nucleoli in the heart and liver cells of the rat. Cancer Res. 36, 1580 - 1584.
77. Miller, O.L. Jr. and Beatty, B.R. (1969). Visualization of nucleolar genes. Science 164, 955 - 957.
78. Narla, A. and Ebert, B.L. (2010). Ribosomopathies: human disorders of ribosome dysfunction. Blood 115, 3196 - 3205.
79. Perry, R.P. (1962). The cellular sites of synthesis of ribosomal and 4S RNA. Proc. Natl. Acad. Sci. USA 48, 2179 - 2186.
80. Pestov, D.G., Strezoska, Z., and Lau, L.F. (2001). Evidence of p53-dependent cross-talk between ribosome biogenesis and the cell cycle: effects of nucleolar protein Bop1 on G(1)/S transition. Mol. Cell. Biol. 21, 4246 - 4255.
81. Phelps, M.A., Lin, T.S., Johnson, A.J., Hurh, E., Rozewski, D.M., Farley, K.L., Wu, D., Blum, K.A., Fischer, B., Mitchell, S.M., et al. (2009). Clinical response and pharmacokinetics from a phase 1 study of an active dosing schedule of flavopiridol in relapsed chronic lymphocytic leukemia. Blood 113, 2637 - 2645.
82. Pondarre, C., Strumberg, D., Fujimori, A., Torres-Leon, R., and Pommier, Y. (1997). In vivo sequencing of camptothecininduced topoisomerase I cleavage sites in human colon carcinoma cells. Nucleic Acids Res. 25, 4111 - 4116.
83. Prieto, J.L. and McStay, B. (2008). Pseudo-NORs: A novel model for studying nucleoli. Biochim. Biophys. Acta 1783, 2116 - 2123.
84. Qi, W., Shakalya, K., Stejskal, A., Goldman, A., Beeck, S., Cooke, L., and Mahadevan, D. (2008). NSC348884, a nucleophosmin inhibitor disrupts oligomer formation and induces apoptosis in human cancer cells. Oncogene 27, 4210 - 4220.
85. Rabani, M., Levin, J.Z., Fan, L., Adiconis, X., Raychowdhury, R., Garber, M., Gnirke, A., Nusbaum, C., Hacohen, N., Friedman, N., et al. (2011). Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells. Nat. Biotechnol. 29, 436- 442.
86. Rey, J.P., Scott, R., and Muller, H. (1993). Induction and removal of interstrand crosslinks in the ribosomal RNA genes of lymphoblastoid cell lines from patients with Fanconi anemia. Mutat. Res. 289, 171 - 180.
87. Ritossa, F.M. and Spiegelman, S. (1965). Localization of Dna complementary to ribosomal RNA in the nucleolus organizer region of Drosophila Melanogaster. Proc. Natl. Acad. Sci. USA 53, 737 - 745.
88. Rohrmoser, M., Holzel, M., Grimm, T., Malamoussi, A., Harasim, T., Orban, M., Pfisterer, I., Gruber-Eber, A., Kremmer, E., and 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.
89. Romanova, L., Grand, A., Zhang, L., Rayner, S., Katoku-Kikyo, N., Kellner, S., and Kikyo, N. (2009). Critical role of nucleostemin in pre-rRNA processing. J. Biol. Chem. 284, 4968-4977.
90. Rubbi, C.P. and Milner, J. (2003). Disruption of the nucleolus mediates stabilization of p53 in response to DNA damage and other stresses. EMBO J. 22, 6068 - 6077.
91. Ruggero, D. (2012). Revisiting the nucleolus: from marker to dynamic integrator of cancer signaling. Sci. Signal. 5, pe38.
92. Ruggero, D., Grisendi, S., Piazza, F., Rego, E., Mari, F., Rao, P.H., Cordon-Cardo, C., and Pandolfi, P.P. (2003). Dyskeratosis congenita and cancer in mice deficient in ribosomal RNA modification. Science 299, 259 - 262.
93. Ruggero, D. and Pandolfi, P.P. (2003). Does the ribosome translate cancer? Nat. Rev. Cancer 3, 179 - 192.
94. Safa, A.R. and Tseng, M.T. (1984). Inhibition of protein synthesis and cell proliferation in cultured human breast cancer cells treated with mitoxantrone. Cancer Lett. 24, 317 - 326.
95. Sakaguchi, K., Herrera, J.E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C.W., and Appella, E. (1998). DNA damage activates p53 through a phosphorylation-acetylation cascade. Genes Dev. 12, 2831- 2841.
96. Sasaki, M., Kawahara, K., Nishio, M., Mimori, K., Kogo, R., Hamada, K., Itoh, B., Wang, J., Komatsu, Y., Yang, Y.R., et al. (2011). Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nat. Med. 17, 944 - 951.
97. Schlosser, I., Holzel, M., Murnseer, M., Burtscher, H., Weidle, U.H., and Eick, D. (2003). A role for c-Myc in the regulation of ribosomal RNA processing. Nucleic Acids Res. 31, 6148 - 6156.
98. Schneider, D.A. (2012). RNA polymerase I activity is regulated at multiple steps in the transcription cycle: recent insights into factors that influence transcription elongation. Gene 493, 176 - 184.
99. Schuhmacher, M., Kohlhuber, F., Holzel, M., Kaiser, C., Burtscher, H., Jarsch, M., Bornkamm, G.W., Laux, G., Polack, A., Weidle, U.H., et al. (2001). The transcriptional program of a human B cell line in response to Myc. Nucleic Acids Res. 29, 397 - 406.
100. Sharpless, N.E. (2005). INK4a/ARF: A multifunctional tumor suppressor locus. Mutat. Res. 576, 22 - 38.
101. Sherr, C.J. and Weber, J.D. (2000). The ARF/p53 pathway. Curr. Opin. Genet. Dev. 10, 94 - 99.
102. Sirri, V., HeRNAndez-Verdun, D., and Roussel, P. (2002). Cyclindependent kinases govern formation and maintenance of the nucleolus. J. Cell. Biol. 156, 969 - 981.
103. Srivastava, L., Lapik, Y.R., Wang, M., and Pestov, D.G. (2010). Mammalian DEAD box protein Ddx51 acts in 3' end maturation of 28S rRNA by promoting the release of U8 snoRNA. Mol. Cell. Biol. 30, 2947 - 2956.
104. Stommel, J.M., Marchenko, N.D., Jimenez, G.S., Moll, U.M., Hope, T.J., and Wahl, G.M. (1999). A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J. 18, 1660- 1672.
105. Tao, W. and Levine, A.J. (1999). P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc. Natl. Acad. Sci. USA 96, 6937 - 6941.
106. Thiry, M., Jamison, J.M., Gilloteaux, J., Summers, J.L., and Goessens, G. (1997). Ultrastructural nucleolar alterations induced by an ametantrone/polyr(A-U) complex. Exp. Cell. Res. 236, 275 - 284.
107. Thomas, G. (2000). An encore for ribosome biogenesis in the control of cell proliferation. Nat. Cell. Biol. 2, E71 - E72.
108. Treiber, D.K., Zhai, X., Jantzen, H.M., and Essigmann, J.M. (1994). Cisplatin-DNA adducts are molecular decoys for the ribosomal RNA transcription factor hUBF (human upstream binding factor). Proc. Natl. Acad. Sci. USA 91, 5672 - 5676.
109. van Riggelen, J., Yetil, A., and Felsher, D.W. (2010). MYC as a regulator of ribosome biogenesis and protein synthesis. Nat. Rev. Cancer 10, 301 - 309.
110. Vassiliou, G.S., Cooper, J.L., Rad, R., Li, J., Rice, S., Uren, A., Rad, L., Ellis, P., Andrews, R., Banerjee, R., et al. (2011). Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nat. Genet. 43, 470 - 475.
111. Vogelstein, B., Lane, D., and Levine, A.J. (2000). Surfing the p53 network. Nature 408, 307 - 310.
112. Vousden, K.H. and Prives, C. (2009). Blinded by the light: the growing complexity of p53. Cell 137, 413 - 431.
113. Wassermann, K., Zwelling, L.A., Mullins, T.D., Silberman, L.E., Andersson, B.S., Bakic, M., Acton, E.M., and Newman, R.A. (1986). Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro. Cancer Res. 46, 4041 - 4046.
114. White, R.J. (2005). RNA polymerases I and III, growth control and cancer. Nat. Rev. Mol. Cell. Biol. 6, 69 - 78.
115. Widmann, B., Wandrey, F., Badertscher, L., Wyler, E., Pfannstiel, J., Zemp, I., and Kutay, U. (2012). The kinase activity of human Rio1 is required for final steps of cytoplasmic maturation of 40S subunits. Mol. Biol. Cell. 23, 22 - 35.
116. Wulff, J.E., Siegrist, R., and Myers, A.G. (2007). The natural product avrainvillamide binds to the oncoprotein nucleophosmin. J. Am. Chem. Soc. 129, 14444 - 14451.
117. Xirodimas, D.P., Stephen, C.W., and Lane, D.P. (2001). Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm2-mediated degradation of p53. Exp. Cell. Res. 270, 66 - 77.
118. Xue, S. and BaRNA, M. (2012). Specialized ribosomes: A new frontier in gene regulation and organismal biology. Nat. Rev. Mol. Cell. Biol. 13, 355 - 369.
119. Yuan, X., Zhou, Y., Casanova, E., Chai, M., Kiss, E., Grone, H.J., Schutz, G., and Grummt, I. (2005). Genetic inactivation of the transcription factor TIF-IA leads to nucleolar disruption, cell cycle arrest, and p53-mediated apoptosis. Mol. Cell. 19, 77 - 87.
120. Zemp, I., Wild, T., O'Donohue, M.F., Wandrey, F., Widmann, B., Gleizes, P.E., and Kutay, U. (2009). Distinct cytoplasmic maturation steps of 40S ribosomal subunit precursors require hRio2. J. Cell. Biol. 185, 1167 - 1180.
121. Zhao, X. and Yu, Y.T. (2007). Incorporation of 5-fluorouracil into U2 snRNA blocks pseudouridylation and pre-mRNA splicing in vivo. Nucleic Acids Res. 35, 550 - 558.