Dysregulation of the basal RNA polymerase transcription apparatus in cancer

Nature Reviews Cancer

Volumn 13, Issue 5, 2013, Pages 299-314

  Bywater, Megan J ^a,b   Pearson, Richard B ^a,b,c   McArthur, Grant A ^a,b,d   Hannan, Ross D ^a,b,c  

^a PETER MACCALLUM CANCER CENTRE   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c MONASH UNIVERSITY   (Australia)

^d UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; BICALUTAMIDE; CISPLATIN; DACTINOMYCIN; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ETOPOSIDE; FLUOROURACIL; FLUTAMIDE; IRINOTECAN; MEDIATOR COMPLEX; MITOMYCIN; RETINOIC ACID; RNA POLYMERASE; TAMOXIFEN; TEMOZOLOMIDE; TOPOTECAN; VORINOSTAT;

APOPTOSIS; BLADDER CANCER; BREAST CANCER; CANCER INCIDENCE; CANCER SUSCEPTIBILITY; CANCER THERAPY; CARCINOGENICITY; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CHROMOSOME 20; COLORECTAL CANCER; COMPLEX FORMATION; DNA BINDING; DNA DAMAGE; DNA SEQUENCE; DNA STRAND; DNA TEMPLATE; DROSOPHILA MELANOGASTER; EXCISION REPAIR; GENE EXPRESSION; HUMAN; INTERACTIONS WITH RNA; LIVER CELL CARCINOMA; LOSS OF FUNCTION MUTATION; LUNG SQUAMOUS CELL CARCINOMA; MALIGNANT TRANSFORMATION; METASTASIS; NEOPLASM; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROMOTER REGION; PROSTATE CANCER; PROTEIN DNA INTERACTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; RNA CLEAVAGE; RNA GENE; RNA SPLICING; RNA SYNTHESIS; RNA TRANSCRIPTION; SIGNAL TRANSDUCTION; TRANSCRIPTION ELONGATION; TRANSCRIPTION INITIATION; TRANSCRIPTION INITIATION SITE; XERODERMA PIGMENTOSUM;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL TRANSFORMATION, NEOPLASTIC; DNA-DIRECTED RNA POLYMERASES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASMS; ONCOGENES; TRANSCRIPTION FACTORS, GENERAL; TRANSCRIPTIONAL ACTIVATION;

EID: 84876884110     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc3496     Document Type: Review

References (190)

1. Roeder, R. G. & Rutter, W. J. Multiple Forms of DNA-Dependent Rna Polymerase in Eukaryotic Organisms. Nature 224, 234-237 (1969).
2. Weinmann, R., Raskas, H. J. & Roeder, R. G. Role of DNA-Dependent Rna Polymerase-Ii and Polymerase-Iii in Transcription of Adenovirus Genome Late in Productive Infection. Proc. Natl Acad. Sci. USA 71, 3426-3430 (1974).
3. Weinmann, R. & Roeder, R. G. Role of DNA-Dependent Rna-Polymerase Iii in Transcription of Transfer-Rna and 5s Rna Genes. Proc. Natl Acad. Sci. USA 71, 1790-1794 (1974).
4. Guttman, M. & Rinn, J. L. Modular regulatory principles of large non-coding RNAs. Nature 482, 339-346 (2012).
5. Esteller, M. Non-coding RNAs in human disease. Nature Rev. Genet. 12, 861-874 (2011).
6. Alexander, R. P., Fang, G., Rozowsky, J., Snyder, M. & Gerstein, M. B. Annotating non-coding regions of the genome. Nature Rev. Genet. 11, 559-571 (2010).
7. Mercer, T. R., Dinger, M. E. & Mattick, J. S. Long non-coding RNAs: insights into functions. Nature Rev. Genet. 10, 155-159 (2009).
8. He, L. & Hannon, G. J. MicroRNAs: small RNAs with a big role in gene regulation. Nature Rev. Genet. 5, 522-531 (2004).
9. White, R. J. Transcription by RNA polymerase III: more complex than we thought. Nature Rev. Genet. 12, 459-463 (2011).
10. Noma, K. & Kamakaka, R. T. The human Pol III transcriptome and gene information flow. Nature Struct. Mol. Biol. 17, 539-541 (2010).
11. Dieci, G., Fiorino, G., Castelnuovo, M., Teichmann, M. & Pagano, A. The expanding RNA polymerase III transcriptome. Trends Genet. 23, 614-622 (2007).
12. Nikitina, T. V., Tischenko, L. I. & Schulz, W. A. Recent insights into regulation of transcription by RNA polymerase III and the cellular functions of its transcripts. Biol. Chem. 392, 395-404 (2011).
13. Sklar, V. E. F., Schwartz, L. B. & Roeder, R. G. Distinct Molecular-Structures of Nuclear Class I, Ii, and Iii DNA-Dependent Rna Polymerases. Proc. Natl Acad. Sci. USA 72, 348-352 (1975).
14. Naidu, S., Friedrich, J. K., Russell, J. & Zomerdijk, J. C. TAF1B is a TFIIB-like component of the basal transcription machinery for RNA polymerase I. Science 333, 1640-1642 (2011).
15. Vannini, A. & Cramer, P. Conservation between the RNA Polymerase I, II, and III Transcription Initiation Machineries. Mol. Cell 45, 439-446 (2012).
16. Cramer, P., et al. Structure of eukaryotic RNA polymerases. Annu. Rev. Biophys. 37, 337-352 (2008).
17. Sekine, S., Tagami, S. & Yokoyama, S. Structural basis of transcription by bacterial and eukaryotic RNA polymerases. Curr. Opin. Struct. Biol. 22, 110-118 (2012).
18. Werner, M., Thuriaux, P. & Soutourina, J. Structure-function analysis of RNA polymerases I and III. Curr. Opin. Struct. Biol. 19, 740-745 (2009).
19. Bywater, M. J., et al. Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53. Cancer Cell 22, 51-65 (2012).
20. Roeder, R. G. The eukaryotic transcriptional machinery: complexities and mechanisms unforeseen. Nature Med. 9, 1239-1244 (2003).
21. Schmitz, K. M., et al. TAF12 recruits Gadd45a and the nucleotide excision repair complex to the promoter of rRNA genes leading to active DNA demethylation. Mol. Cell 33, 344-353 (2009).
22. Drygin, D., et al. Targeting RNA polymerase I with an oral small molecule CX5461 inhibits ribosomal RNA synthesis and solid tumor growth. Cancer Res. 71, 1418-1430 (2011).
23. Compe, E. & Egly, J. M. TFIIH: when transcription met DNA repair. Nature Rev. Mol. Cell Biol. 13, 343-354 (2012).
24. Iben, S., et al. TFIIH plays an essential role in RNA polymerase I transcription. Cell 109, 297-306 (2002).
25. Bradsher, J., et al. CSB is a component of RNA pol I transcription. Mol. Cell 10, 819-829 (2002).
26. Assfalg, R., et al. TFIIH is an elongation factor of RNA polymerase I. Nucleic Acids Res. 40, 650-659 (2012).
27. Egly, J. M. & Coin, F. A history of TFIIH: two decades of molecular biology on a pivotal transcription/repair factor. DNA Repair (Amst.) 10, 714-721 (2011).
28. Wang, F., et al. DNA repair gene XPD polymorphisms and cancer risk: a meta-analysis based on 56 case-control studies. Cancer Epidemiol. Biomarkers Prev. 17, 507-517 (2008).
29. Manuguerra, M., et al. XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. Am. J. Epidemiol. 164, 297-302 (2006).
30. Xue, H., et al. The effect of XPD/ERCC2 polymorphisms on gastric cancer risk among different ethnicities: a systematic review and meta-analysis. PLoS ONE 7, e43431 (2012).
31. Johnson, S. A., et al. Increased expression of TATA-binding protein, the central transcription factor, can contribute to oncogenesis. Mol. Cell. Biol. 23, 3043-3051 (2003).
32. Li, B. Q., Huang, T., Liu, L., Cai, Y. D. & Chou, K. C. Identification of colorectal cancer related genes with mRMR and shortest path in protein-protein interaction network. PLoS ONE 7, e33393 (2012).
33. Daly, N. L., et al. Deregulation of RNA polymerase III transcription in cervical epithelium in response to high-risk human papillomavirus. Oncogene 24, 880-888 (2005).
34. Lockwood, W. W., et al. Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma. PLoS Med. 7, e1000315 (2010).
35. Zhong, S., Zhang, C. & Johnson, D. L. Epidermal growth factor enhances cellular TATA binding protein levels and induces RNA polymerase I-and III-dependent gene activity. Mol. Cell. Biol. 24, 5119-5129 (2004).
36. Colgan, J. & Manley, J. L. TFIID can be rate limiting in vivo for TATA-containing, but not TATA-lacking, RNA polymerase II promoters. Genes Dev. 6, 304-315 (1992).
37. Majello, B., Napolitano, G., De Luca, P. & Lania, L. Recruitment of human TBP selectively activates RNA polymerase II TATA-dependent promoters. J. Biol. Chem. 273, 16509-16516 (1998).
38. Johnson, S. A., Dubeau, L. & Johnson, D. L. Enhanced RNA polymerase III-dependent transcription is required for oncogenic transformation. J. Biol. Chem. 283, 19184-19191 (2008).
39. Trivedi, A., Vilalta, A., Gopalan, S. & Johnson, D. L. TATA-binding protein is limiting for both TATA-containing and TATA-lacking RNA polymerase III promoters in Drosophila cells. Mol. Cell. Biol. 16, 6909-6916 (1996).
40. Wang, H. D., Trivedi, A. & Johnson, D. L. Regulation of RNA polymerase I-dependent promoters by the hepatitis B virus X protein via activated Ras and TATA-binding protein. Mol. Cell. Biol. 18, 7086-7094 (1998).
41. Sadovsky, Y., et al. Transcriptional activators differ in their responses to overexpression of TATA-box-binding protein. Mol. Cell. Biol. 15, 1554-1563 (1995).
42. Dauwerse, J. G., et al. Mutations in genes encoding subunits of RNA polymerases I and III cause Treacher Collins syndrome. Nature Genet. 43, 20-22 (2011).
43. Poortinga, G., et al. c-MYC coordinately regulates ribosomal gene chromatin remodeling and Pol I availability during granulocyte differentiation. Nucleic Acids Res. 39, 3267-3281 (2011).
44. Winter, A. G., et al. RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors. Proc. Natl Acad. Sci. USA 97, 12619-12624 (2000).
45. Garcia, M. J., et al. A 1 Mb minimal amplicon at 8p1112 in breast cancer identifies new candidate oncogenes. Oncogene 24, 5235-5245 (2005).
46. Melchor, L., et al. Genomic analysis of the 8p1112 amplicon in familial breast cancer. Int. J. Cancer 120, 714-717 (2007).
47. Williams, S. V., et al. High-resolution analysis of genomic alteration on chromosome arm 8p in urothelial carcinoma. Genes Chromosomes Cancer 49, 642-659 (2010).
48. Cabarcas, S. & Schramm, L. RNA polymerase III transcription in cancer: the BRF2 connection. Mol. Cancer 10, 47 (2011).
49. Schramm, L. & Hernandez, N. Recruitment of RNA polymerase III to its target promoters. Genes Dev. 16, 2593-2620 (2002).
50. Huang, Y. & Maraia, R. J. Comparison of the RNA polymerase III transcription machinery in Schizosaccharomyces pombe, Saccharomyces cerevisiae and human. Nucleic Acids Res. 29, 2675-2690 (2001).
51. Geiduschek, E. P. & Kassavetis, G. A. The RNA polymerase III transcription apparatus. J. Mol. Biol. 310, 1-26 (2001).
52. Boeger, H., et al. Structural basis of eukaryotic gene transcription. FEBS Lett. 579, 899-903 (2005).
53. White, R. J. RNA polymerases I and III, non-coding RNAs and cancer. Trends Genet. 24, 622-629 (2008).
54. Kelleher, R. J., 3rd, Flanagan, P. M. & Kornberg, R. D. A novel mediator between activator proteins and the RNA polymerase II transcription apparatus. Cell 61, 1209-1215 (1990).
55. Kim, Y. J., Bjorklund, S., Li, Y., Sayre, M. H. & Kornberg, R. D. A multiprotein mediator of transcriptional activation and its interaction with the C-terminal repeat domain of RNA polymerase II. Cell 77, 599-608 (1994).
56. Chao, D. M., et al. A mammalian SRB protein associated with an RNA polymerase II holoenzyme. Nature 380, 82-85 (1996).
57. Malik, S. & Roeder, R. G. Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem. Sci. 30, 256-263 (2005).
58. Conaway, R. C., Sato, S., Tomomori-Sato, C., Yao, T. & Conaway, J. W. The mammalian Mediator complex and its role in transcriptional regulation. Trends Biochem. Sci. 30, 250-255 (2005).
59. Kornberg, R. D. Mediator and the mechanism of transcriptional activation. Trends Biochem. Sci. 30, 235-239 (2005).
60. Lee, T. I. & Young, R. A. Transcription of eukaryotic protein-coding genes. Annu. Rev. Genet. 34, 77-137 (2000).
61. Boube, M., Joulia, L., Cribbs, D. L. & Bourbon, H. M. Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man. Cell 110, 143-151 (2002).
62. Sato, S., et al. A set of consensus mammalian mediator subunits identified by multidimensional protein identification technology. Mol. Cell 14, 685-691 (2004).
63. Bourbon, H. M. Comparative genomics supports a deep evolutionary origin for the large, four-module transcriptional mediator complex. Nucleic Acids Res. 36, 3993-4008 (2008).
64. Malik, S. & Roeder, R. G. The metazoan Mediator co-activator complex as an integrative hub for transcriptional regulation. Nature Rev. Genet. 11, 761-772 (2010).
65. Takahashi, H., et al. Human mediator subunit MED26 functions as a docking site for transcription elongation factors. Cell 146, 92-104 (2011).
66. Zhou, Q., Li, T. & Price, D. H. RNA Polymerase II Elongation Control. Annu Rev. Biochem. 81, 119-143 (2012).
67. Conaway, R. C. & Conaway, J. W. The Mediator complex and transcription elongation. Biochim. Biophys. Acta 1829, 69-75 (2013).
68. Napoli, C., Sessa, M., Infante, T. & Casamassimi, A. Unraveling framework of the ancestral Mediator complex in human diseases. Biochimie 94, 579-587 (2012).
69. Firestein, R., et al. CDK8 is a colorectal cancer oncogene that regulates beta-catenin activity. Nature 455, 547-551 (2008).
70. Firestein, R. & Hahn, W. C. Revving the Throttle on an oncogene: CDK8 takes the driver seat. Cancer Res. 69, 7899-7901 (2009).
71. Chen, W. & Roeder, R. G. Mediator-dependent nuclear receptor function. Semin. Cell Dev. Biol. 22, 749-758 (2011).
72. Ito, M., et al. Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators. Mol. Cell 3, 361-370 (1999).
73. Gu, W., et al. A novel human SRB/MED-containing cofactor complex, SMCC, involved in transcription regulation. Mol. Cell 3, 97-108 (1999).
74. Rachez, C., et al. A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system. Genes Dev. 12, 1787-1800 (1998).
75. Yuan, C. X., Ito, M., Fondell, J. D., Fu, Z. Y. & Roeder, R. G. The TRAP220 component of a thyroid hormone receptor-associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion. Proc. Natl Acad. Sci. USA 95, 7939-7944 (1998).
76. Kang, Y. K., Guermah, M., Yuan, C. X. & Roeder, R. G. The TRAP/mediator coactivator complex interacts directly with estrogen receptors alpha and beta through the TRAP220 subunit and directly enhances estrogen receptor function in vitro. Proc. Natl Acad. Sci. USA 99, 2642-2647 (2002).
77. Jia, Y., et al. Transcription coactivator PBP, the peroxisome proliferator-activated receptor (PPAR)-binding protein, is required for PPARalpha-regulated gene expression in liver. J. Biol. Chem. 279, 24427-24434 (2004).
78. Zhang, X. T., et al. MED1/TRAP220 exists predominantly in a TRAP/mediator subpopulation enriched in RNA polymerase II and is required for ER-mediated transcription. Mol. Cell 19, 89-100 (2005).
79. Vijayvargia, R., May, M. S. & Fondell, J. D. A coregulatory role for the mediator complex in prostate cancer cell proliferation and gene expression. Cancer Res. 67, 4034-4041 (2007).
80. Lamy, P. J., et al. Quantification and clinical relevance of gene amplification at chromosome 17q12q21 in human epidermal growth factor receptor 2amplified breast cancers. Breast Cancer Res. 13, R15 (2011).
81. Nagalingam, A., et al. Med1 plays a critical role in the development of tamoxifen resistance. Carcinogenesis 33, 918-930 (2012).
82. Cui, J., et al. Cross-talk between HER2 and MED1 regulates tamoxifen resistance of human breast cancer cells. Cancer Res. 72, 5625-5634 (2012).
83. Kim, H. J., et al. Loss of Med1/TRAP220 promotes the invasion and metastasis of human non-small-cell lung cancer cells by modulating the expression of metastasis-related genes. Cancer Lett. 321, 195-202 (2012).
84. Barbieri, C. E., et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nature Genet. 44, 685-689 (2012).
85. Li, L. H., He, J., Hua, D., Guo, Z. J. & Gao, Q. Lentivirus-mediated inhibition of Med19 suppresses growth of breast cancer cells in vitro. Cancer Chemother. Pharmacol. 68, 207-215 (2011).
86. Sun, M., et al. MED19 promotes proliferation and tumorigenesis of lung cancer. Mol. Cell Biochem. 355, 27-33 (2011).
87. Zou, S. W., et al. The role of Med19 in the proliferation and tumorigenesis of human hepatocellular carcinoma cells. Acta Pharmacol. Sin. 32, 354-360 (2011).
88. Zhang, H., et al. Expression of Med19 in bladder cancer tissues and its role on bladder cancer cell growth. Urol. Oncol. 30, 920-927 (2012).
89. Kuuselo, R., et al. Intersex-like (IXL) is a cell survival regulator in pancreatic cancer with 19q13 amplification. Cancer Res. 67, 1943-1949 (2007).
90. Chen, S., et al. Copy number alterations in pancreatic cancer identify recurrent PAK4 amplification. Cancer Biol. Ther. 7, 1793-1802 (2008).
91. Kuuselo, R., Savinainen, K., Sandstrom, S., Autio, R. & Kallioniemi, A. MED29, a component of the mediator complex, possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer. Int. J. Cancer 129, 2553-2565 (2011).
92. Boyer, T. G., Martin, M. E., Lees, E., Ricciardi, R. P. & Berk, A. J. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature 399, 276-279 (1999).
93. Blattner, C., et al. Molecular basis of Rrn3regulated RNA polymerase I initiation and cell growth. Genes Dev. 25, 2093-2105 (2011).
94. Soutourina, J., Wydau, S., Ambroise, Y., Boschiero, C. & Werner, M. Direct interaction of RNA polymerase II and mediator required for transcription in vivo. Science 331, 1451-1454 (2011).
95. Takagi, Y., et al. Head module control of mediator interactions. Mol. Cell 23, 355-364 (2006).
96. Zhao, J., Yuan, X., Frodin, M. & Grummt, I. ERK-dependent phosphorylation of the transcription initiation factor TIF-IA is required for RNA polymerase I transcription and cell growth. Mol. Cell 11, 405-413 (2003).
97. Mayer, C. Zhao, J., Yuan, X. & Grummt, I. mTOR-dependent activation of the transcription factor TIF-IA links rRNA synthesis to nutrient availability. Genes Dev. 18, 423-434 (2004).
98. Hoppe, S., et al. AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply. Proc. Natl Acad. Sci. USA 106, 17781-17786 (2009).
99. Bierhoff, H., Dundr, M., Michels, A. A. & Grummt, I. Phosphorylation by casein kinase 2 facilitates rRNA gene transcription by promoting dissociation of TIF-IA from elongating RNA polymerase I. Mol. Cell. Biol. 28, 4988-4998 (2008).
100. Johnson, S. S., Zhang, C., Fromm, J., Willis, I. M. & Johnson, D. L. Mammalian Maf1 is a negative regulator of transcription by all three nuclear RNA polymerases. Mol. Cell 26, 367-379 (2007).
101. Willis, I. M. & Moir, R. D. Integration of nutritional and stress signaling pathways by Maf1. Trends Biochem. Sci. 32, 51-53 (2007).
102. Wei, Y. & Zheng, X. S. Maf1 regulation: a model of signal transduction inside the nucleus. Nucleus 1, 162-165 (2010).
103. Gilchrist, D. A., et al. Pausing of RNA polymerase II disrupts DNA-specified nucleosome organization to enable precise gene regulation. Cell 143, 540-551 (2010).
104. Phatnani, H. P. & Greenleaf, A. L. Phosphorylation & functions of the R. N. A. polymerase I. I. C. T. D. Genes Dev. 20, 2922-2936 (2006).
105. Yamada, T., et al. P-TEFb-mediated phosphorylation of hSpt5 C-terminal repeats is critical for processive transcription elongation. Mol. Cell 21, 227-237 (2006).
106. Gilmour, D. S. & Lis, J. T. RNA polymerase II interacts with the promoter region of the noninduced hsp70 gene in Drosophila melanogaster cells. Mol. Cell. Biol. 6, 3984-3989 (1986).
107. Rougvie, A. E. & Lis, J. T. The RNA polymerase II molecule at the 5' end of the uninduced hsp70 gene of D. melanogaster is transcriptionally engaged. Cell 54, 795-804 (1988).
108. Krumm, A., Meulia, T., Brunvand, M. & Groudine, M. The block to transcriptional elongation within the human c-myc gene is determined in the promoter-proximal region. Genes Dev. 6, 2201-2213 (1992).
109. Plet, A., Eick, D. & Blanchard, J. M. Elongation and premature termination of transcripts initiated from c-fos and c-myc promoters show dissimilar patterns. Oncogene 10, 319-328 (1995).
110. Zeitlinger, J., et al. RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nature Genet. 39, 1512-1516 (2007).
111. Muse, G. W., et al. RNA polymerase is poised for activation across the genome. Nature Genet. 39, 1507-1511 (2007).
112. Gilchrist, D. A., et al. NELF-mediated stalling of Pol II can enhance gene expression by blocking promoter-proximal nucleosome assembly. Genes Dev. 22, 1921-1933 (2008).
113. Nechaev, S., et al. Global analysis of short RNAs reveals widespread promoter-proximal stalling and arrest of Pol II in Drosophila. Science 327, 335-338 (2010).
114. Singh, J. & Padgett, R. A. Rates of in situ transcription and splicing in large human genes. Nature Struct. Mol. Biol. 16, 1128-1133 (2009).
115. Orphanides, G., LeRoy, G., Chang, C. H., Luse, D. S. & Reinberg, D. FACT, a factor that facilitates transcript elongation through nucleosomes. Cell 92, 105-116 (1998).
116. Belotserkovskaya, R., et al. FACT facilitates transcription-dependent nucleosome alteration. Science 301, 1090-1093 (2003).
117. Orphanides, G., Wu, W. H., Lane, W. S., Hampsey, M. & Reinberg, D. The chromatin-specific transcription elongation factor FACT comprises human SPT16 and SSRP1 proteins. Nature 400, 284-288 (1999).
118. Smith, E., Lin, C. & Shilatifard, A. The super elongation complex (SEC) and MLL in development and disease. Genes Dev. 25, 661-672 (2011).
119. Daser, A. & Rabbitts, T. H. The versatile mixed lineage leukaemia gene MLL and its many associations in leukaemogenesis. Semin. Cancer Biol. 15, 175-188 (2005).
120. Luo, Z., Lin, C. & Shilatifard, A. The super elongation complex (SEC) family in transcriptional control. Nature Rev. Mol. Cell Biol. 13, 543-547 (2012).
121. Xu, Q., Nakanishi, T., Sekimizu, K. & Natori, S. Cloning and identification of testis-specific transcription elongation factor S-II. J. Biol. Chem. 269, 3100-3103 (1994).
122. Labhart, P. & Morgan, G. T. Identification of novel genes encoding transcription elongation factor TFIIS (TCEA) in vertebrates: conservation of three distinct TFIIS isoforms in frog, mouse, and human. Genomics 52, 278-288 (1998).
123. Shema, E., Kim, J., Roeder, R. G. & Oren, M. RNF20 inhibits TFIIS-facilitated transcriptional elongation to suppress pro-oncogenic gene expression. Mol. Cell 42, 477-488 (2011).
124. Scotto, L., et al. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer 47, 755-765 (2008).
125. Hubbard, K., Catalano, J., Puri, R. K. & Gnatt, A. Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis. BMC Cancer 8, 133 (2008).
126. Yoshida, K., et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478, 64-69 (2011).
127. Visconte, V., Makishima, H., Maciejewski, J. P. & Tiu, R. V. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders. Leukemia 26, 2447-2454 (2012).
128. Morris, A. R., et al. Alternative cleavage and polyadenylation during colorectal cancer development. Clin. Cancer Res. 18, 5256-5266 (2012).
129. Mayr, C. & Bartel, D. P. Widespread shortening of 3'UTRs by alternative cleavage and polyadenylation activates oncogenes in cancer cells. Cell 138, 673-684 (2009).
130. Singh, P., et al. Global changes in processing of mRNA 3' untranslated regions characterize clinically distinct cancer subtypes. Cancer Res. 69, 9422-9430 (2009).
131. Kaida, D., Schneider-Poetsch, T. & Yoshida, M. Splicing in oncogenesis and tumor suppression. Cancer Sci. 103, 1611-1616 (2012).
132. Ghavi-Helm, Y., et al. Genome-wide location analysis reveals a role of TFIIS in RNA polymerase III transcription. Genes Dev. 22, 1934-1947 (2008).
133. Birch, J. L., et al. FACT facilitates chromatin transcription by RNA polymerases I and III. EMBO J. 28, 854-865 (2009).
134. Stefanovsky, V., Langlois, F., Gagnon-Kugler, T., Rothblum, L. I. & Moss, T. Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol. Cell 21, 629-639 (2006).
135. Chan, J. C., et al. AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome biogenesis in cancer. Sci Signal 4, ra56 (2011).
136. Robinson, M. J. & Cobb, M. H. Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol. 9, 180-186 (1997).
137. Poortinga, G., et al. MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation. EMBO J. 23, 3325-3335 (2004).
138. Huang, R., et al. Upstream binding factor up-regulated in hepatocellular carcinoma is related to the survival and cisplatin-sensitivity of cancer cells. FASEB J. 16, 293-301 (2002).
139. Hannan, K. M., et al. mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF. Mol. Cell. Biol. 23, 8862-8877 (2003).
140. Schneider, D. A. 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 (2012).
141. Anderson, S. J., et al. The transcription elongation factor Spt5 influences transcription by RNA polymerase I positively and negatively. J. Biol. Chem. 286, 18816-18824 (2011).
142. Viktorovskaya, O. V., Appling, F. D. & Schneider, D. A. Yeast transcription elongation factor Spt5 associates with RNA polymerase I and RNA polymerase II directly. J. Biol. Chem. 286, 18825-18833 (2011).
143. Zhang, Y., Sikes, M. L., Beyer, A. L. & Schneider, D. A. The Paf1 complex is required for efficient transcription elongation by RNA polymerase I. Proc. Natl Acad. Sci. USA 106, 2153-2158 (2009).
144. Drygin, D., Rice, W. G. & Grummt, I. The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer. Annu. Rev. Pharmacol. Toxicol. 50, 131-156 (2010).
145. Darnell, J. E. Jr. Transcription factors as targets for cancer therapy. Nature Rev. Cancer 2, 740-749 (2002).
146. Koehler, A. N. A complex task? Direct modulation of transcription factors with small molecules. Curr. Opin. Chem. Biol. 14, 331-340 (2010).
147. Morishita, R., et al. In vivo transfection of cis element "decoy" against nuclear factor-kappaB binding site prevents myocardial infarction. Nature Med. 3, 894-899 (1997).
148. De Stefano, D., De Rosa, G. & Carnuccio, R. NFkappaB decoy oligonucleotides. Curr. Opin. Mol. Ther. 12, 203-213 (2010).
149. Gambari, R. New trends in the development of transcription factor decoy (TFD) pharmacotherapy. Curr. Drug Targets 5, 419-430 (2004).
150. De Stefano, D. Oligonucleotides decoy to NF-kappaB: becoming a reality? Discov. Med. 12, 97-105 (2011).
151. Koh, J. T. & Zheng, J. The new biomimetic chemistry: artificial transcription factors. ACS Chem. Biol. 2, 599-601 (2007).
152. Jamieson, A. C., Miller, J. C. & Pabo, C. O. Drug discovery with engineered zinc-finger proteins. Nature Rev. Drug Discov. 2, 361-368 (2003).
153. Bogdanove, A. J. & Voytas, D. F. TAL effectors: customizable proteins for DNA targeting. Science 333, 1843-1846 (2011).
154. Zhang, F., et al. Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nature Biotechnol. 29, 149-153 (2011).
155. Boch, J., et al. Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509-1512 (2009).
156. Krystof, V., Baumli, S. & Furst, R. Perspective of cyclin-dependent kinase 9 (CDK9) as a drug target. Curr. Pharm. Des. 18, 2883-2890 (2012).
157. Godley, L. A. & Larson, R. A. Therapy-related myeloid leukemia. Semin. Oncol. 35, 418-429 (2008).
158. Hijiya, N., Ness, K. K., Ribeiro, R. C. & Hudson, M. M. Acute leukemia as a secondary malignancy in children and adolescents: current findings and issues. Cancer 115, 23-35 (2009).
159. Boutet, S., et al. High-resolution protein structure determination by serial femtosecond crystallography. Science 337, 362-364 (2012).
160. Zhai, W. & Comai, L. Repression of RNA polymerase I transcription by the tumor suppressor p53. Mol. Cell. Biol. 20, 5930-5938 (2000).
161. Crighton, D., et al. p53 represses RNA polymerase III transcription by targeting TBP and inhibiting promoter occupancy by TFIIIB. EMBO J. 22, 2810-2820 (2003).
162. Budde, A. & Grummt, I. p53 represses ribosomal gene transcription. Oncogene 18, 1119-1124 (1999).
163. Stein, T., Crighton, D., Boyle, J. M., Varley, J. M. & White, R. J. RNA polymerase III transcription can be derepressed by oncogenes or mutations that compromise p53 function in tumours and Li-Fraumeni syndrome. Oncogene 21, 2961-2970 (2002).
164. Grewal, S. S., Li, L., Orian, A., Eisenman, R. N. & Edgar, B. A. Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nature Cell Biol. 7, 295-302 (2005).
165. Arabi, A., et al. c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Nature Cell Biol. 7, 303-310 (2005).
166. Grandori, C., et al. c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nature Cell Biol. 7, 311-318 (2005).
167. Shiue, C. N., Berkson, R. G. & Wright, A. P. c-Myc induces changes in higher order rDNA structure on stimulation of quiescent cells. Oncogene 28, 1833-1842 (2009).
168. Kenneth, N. S., et al. TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription. Proc. Natl Acad. Sci. USA 104, 14917-14922 (2007).
169. Jordan, P. & Carmo-Fonseca, M. Molecular mechanisms involved in cisplatin cytotoxicity. Cell. Mol. Life Sci. 57, 1229-1235 (2000).
170. Siddik, Z. H. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279 (2003).
171. Gniazdowski, M., Denny, W. A., Nelson, S. M. & Czyz, M. Transcription factors as targets for DNA-interacting drugs. Curr. Med. Chem. 10, 909-924 (2003).
172. Longley, D. B., Harkin, D. P. & Johnston, P. G. 5fluorouracil: mechanisms of action and clinical strategies. Nature Rev. Cancer 3, 330-338 (2003).
173. Ghoshal, K. & Jacob, S. T. Specific inhibition of pre-ribosomal RNA processing in extracts from the lymphosarcoma cells treated with 5fluorouracil. Cancer Res. 54, 632-636 (1994).
174. Iapalucci-Espinoza, S. & Franze-Fernandez, M. T. Effect of protein synthesis inhibitors and low concentrations of actinomycin D on ribosomal RNA synthesis. FEBS Lett. 107, 281-284 (1979).
175. Lempiainen, H. & Shore, D. Growth control and ribosome biogenesis. Curr. Opin. Cell Biol. 21, 855-863 (2009).
176. Granneman, S. & Baserga, S. J. Ribosome biogenesis: of knobs and RNA processing. Exp. Cell Res. 296, 43-50 (2004).
177. Moss, T., Langlois, F., Gagnon-Kugler, T. & Stefanovsky, V. A housekeeper with power of attorney: the rRNA genes in ribosome biogenesis. Cell. Mol. Life Sci. 64, 29-49 (2007).
178. Russell, J. & Zomerdijk, J. C. RNA-polymerase-I-directed rDNA transcription, life and works. Trends Biochem. Sci. 30, 87-96 (2005).
179. Hernandez-Verdun, D. Assembly and disassembly of the nucleolus during the cell cycle. Nucleus 2, 189-194 (2011).
180. McStay, B. & Grummt, I. The epigenetics of rRNA genes: from molecular to chromosome biology. Annu. Rev. Cell Dev. Biol. 24, 131-157 (2008).
181. Ruggero, D. & Pandolfi, P. P. Does the ribosome translate cancer? Nature Rev. Cancer 3, 179-192 (2003).
182. Derenzini, M., Montanaro, L. & Trere, D. What the nucleolus says to a tumour pathologist. Histopathology 54, 753-762 (2009).
183. Boisvert, F. M., van Koningsbruggen, S., Navascues, J. & Lamond, A. I. The multifunctional nucleolus. Nature Rev. Mol. Cell Biol. 8, 574-585 (2007).
184. Pederson, T. The nucleolus. Cold Spring Harb. Perspect. Biol. 1 Mar 2011 (doi:10.1101/cshperspect. a000638).
185. Ruggero, D. Revisiting the nucleolus: from marker to dynamic integrator of cancer signaling. Sci Signal 5, pe38 (2012).
186. Boulon, S., Westman, B. J., Hutten, S., Boisvert, F. M. & Lamond, A. I. The nucleolus under stress. Mol. Cell 40, 216-227 (2010).
187. Deisenroth, C. & Zhang, Y. Ribosome biogenesis surveillance: probing the ribosomal proteinMdm2p53 pathway. Oncogene 29, 4253-4260 (2010).
188. Fumagalli, S., et al. Absence of nucleolar disruption after impairment of 40S ribosome biogenesis reveals an rpL11translation-dependent mechanism of p53 induction. Nature Cell Biol. 11, 501-508 (2009).
189. Russell, J. & Zomerdijk, J. C. The RNA polymerase I transcription machinery. Biochem. Soc. symp. 203-216 (2006).
190. Roeder, R. G. Lasker Basic Medical Research Award. The eukaryotic transcriptional machinery: complexities and mechanisms unforeseen. Nature Med. 9, 1239-1244 (2003).