Arginine methyltransferases as novel therapeutic targets for breast cancer

Mutagenesis

Volumn 30, Issue 2, 2015, Pages 177-189

  Morettin, Alan ^a   Mitchell Baldwin, R ^a   Côté, Jocelyn ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

2,5 BIS(4 AMIDINOPHENYL)FURAN; 4 HYDROXYBENZOIC ACID; ALLANTODAPSONE; ANTINEOPLASTIC AGENT; CHLORDECONE; LICOCHALCONE A; METHYLTRANSFERASE INHIBITOR; PROTEIN ARGININE METHYLTRANSFERASE; PROTEIN ARGININE METHYLTRANSFERASE 1; PROTEIN ARGININE METHYLTRANSFERASE 2; PROTEIN ARGININE METHYLTRANSFERASE 3; PROTEIN ARGININE METHYLTRANSFERASE 4; PROTEIN ARGININE METHYLTRANSFERASE 5; PROTEIN ARGININE METHYLTRANSFERASE 6; PROTEIN ARGININE METHYLTRANSFERASE 7; PROTEIN ARGININE METHYLTRANSFERASE INHIBITOR; STILBAMIDINE; TAMOXIFEN; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; BREAST CANCER; BREAST CARCINOGENESIS; DNA REPAIR; DRUG TARGETING; ENZYME ACTIVITY; HUMAN; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN METHYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; RNA METABOLISM; SIGNAL TRANSDUCTION; ANTAGONISTS AND INHIBITORS; BREAST NEOPLASMS; ENZYMOLOGY; FEMALE; PHYSIOLOGY;

ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; FEMALE; HUMANS; PROTEIN-ARGININE N-METHYLTRANSFERASES;

EID: 84929656281     PISSN: 02678357     EISSN: 14643804     Source Type: Journal    
DOI: 10.1093/mutage/geu039     Document Type: Review

References (209)

1. Ferlay, J., Soerjomataram, I., Ervik, M et al. (2013) Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11.
2. Hanahan, D. and Weinberg, R. A. (2000) The hallmarks of cancer. Cell, 100, 57-70.
3. Bedford, M. T. and Richard, S. (2005) Arginine methylation an emerging regulator of protein function. Mol. Cell, 18, 263-272.
4. Tripsianes, K., Madl, T., Machyna, M., Fessas, D., Englbrecht, C., Fischer, U., Neugebauer, K. M. and Sattler, M. (2011) Structural basis for dimethy-larginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat. Struct. Mol. Biol., 18, 1414-1420.
5. Katz, J. E., Dlakic, M. and Clarke, S. (2003) Automated identifcation of putative methyltransferases from genomic open reading frames. Mol. Cell. Proteomics, 2, 525-540.
6. Cheng, X., Collins, R. E. and Zhang, X. (2005) Structural and sequence motifs of protein (histone) methylation enzymes. Annu. Rev. Biophys. Bio-mol. Struct., 34, 267-294.
7. Zurita-Lopez, C. I., Sandberg, T., Kelly, R. and Clarke, S. G. (2012) Human protein arginine methyltransferase 7 (PRMT7) is a type III enzyme forming ω-NG-monomethylated arginine residues. J. Biol. Chem., 287, 7859-7870.
8. Lee, J., Sayegh, J., Daniel, J., Clarke, S. and Bedford, M. T. (2005) PRMT8, a new membrane-bound tissue-specifc member of the protein arginine methyltransferase family. J. Biol. Chem., 280, 32890-32896.
9. Boffa, L. C., Karn, J., Vidali, G. and Allfrey, V. G. (1977) Distribution of NG, NG,-dimethylarginine in nuclear protein fractions. Biochem. Bio-phys. Res. Commun., 74, 969-976.
10. Lee, J. and Bedford, M. T. (2002) PABP1 identifed as an arginine meth-yltransferase substrate using high-density protein arrays. EMBO Rep., 3, 268-273.
11. Feng, Y., Maity, R., Whitelegge, J. P., et al. (2013) Mammalian protein arginine methyltransferase 7 (PRMT7) specifcally targets RXR sites in lysine-and arginine-rich regions. J. Biol. Chem., 288, 37010-37025.
12. Cheng, D., Côté, J., Shaaban, S. and Bedford, M. T. (2007) The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol. Cell, 25, 71-83.
13. Branscombe, T. L., Frankel, A., Lee, J. H., Cook, J. R., Yang, Z., Pestka, S. and Clarke, S. (2001) PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins. J. Biol. Chem., 276, 32971-32976.
14. Frankel, A., Yadav, N., Lee, J., Branscombe, T. L., Clarke, S. and Bedford, M. T. (2002) The novel human protein arginine N-methyltransferase PRMT6 is a nuclear enzyme displaying unique substrate specifcity. J. Biol. Chem., 277, 3537-3543.
15. Sgarra, R., Lee, J., Tessari, M. A., Altamura, S., Spolaore, B., Giancotti, V., Bedford, M. T. and Manfoletti, G. (2006) The AT-hook of the chromatin architectural transcription factor high mobility group A1a is arginine-methylated by protein arginine methyltransferase 6. J. Biol. Chem., 281, 3764-3772.
16. El-Andaloussi, N., Valovka, T., Toueille, M., et al. (2006) Arginine meth-ylation regulates DNA polymerase beta. Mol. Cell, 22, 51-62.
17. Boulanger, M. C., Liang, C., Russell, R. S., Lin, R., Bedford, M. T., Wainberg, M. A. and Richard, S. (2005) Methylation of Tat by PRMT6 regulates human immunodefciency virus type 1 gene expression. J. Virol., 79, 124-131.
18. Hong, H., Kao, C., Jeng, M. H., et al. (2004) Aberrant expression of CARM1, a transcriptional coactivator of androgen receptor, in the development of prostate carcinoma and androgen-independent status. Cancer, 101, 83-89.
19. Cheung, N., Chan, L. C., Thompson, A., Cleary, M. L. and So, C. W. (2007) Protein arginine-methyltransferase-dependent oncogenesis. Nat. Cell Biol., 9, 1208-1215.
20. Kim, Y. R., Lee, B. K., Park, R. Y., Nguyen, N. T., Bae, J. A., Kwon, D. D. and Jung, C. (2010) Differential CARM1 expression in prostate and colo-rectal cancers. BMC Cancer, 10, 197.
21. Mathioudaki, K., Papadokostopoulou, A., Scorilas, A., Xynopoulos, D., Agnanti, N. and Talieri, M. (2008) The PRMT1 gene expression pattern in colon cancer. Br. J. Cancer, 99, 2094-2099.
22. Mathioudaki, K., Scorilas, A., Ardavanis, A., Lymberi, P., Tsiambas, E., Devetzi, M., Apostolaki, A. and Talieri, M. (2011) Clinical evaluation of PRMT1 gene expression in breast cancer. Tumour Biol., 32, 575-582.
23. Papadokostopoulou, A., Mathioudaki, K., Scorilas, A., Xynopoulos, D., Ardavanis, A., Kouroumalis, E. and Talieri, M. (2009) Colon cancer and protein arginine methyltransferase 1 gene expression. Anticancer Res., 29, 1361-1366.
24. Pal, S., Baiocchi, R. A., Byrd, J. C., Grever, M. R., Jacob, S. T. and Sif, S. (2007) Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma. EMBO J., 26, 3558-3569.
25. Pahlich, S., Zakaryan, R. P. and Gehring, H. (2006) Protein arginine meth-ylation: Cellular functions and methods of analysis. Biochim. Biophys. Acta, 1764, 1890-1903.
26. Tang, J., Frankel, A., Cook, R. J., Kim, S., Paik, W. K., Williams, K. R., Clarke, S. and Herschman, H. R. (2000) PRMT1 is the predominant type I protein arginine methyltransferase in mammalian cells. J. Biol. Chem., 275, 7723-7730.
27. Pawlak, M. R., Scherer, C. A., Chen, J., Roshon, M. J. and Ruley, H. E. (2000) Arginine N-methyltransferase 1 is required for early postimplanta-tion mouse development, but cells defcient in the enzyme are viable. Mol. Cell. Biol., 20, 4859-4869.
28. Nicholson, T. B., Chen, T. and Richard, S. (2009) The physiological and pathophysiological role of PRMT1-mediated protein arginine methyla-tion. Pharmacol. Res., 60, 466-474.
29. Strahl, B. D., Briggs, S. D., Brame, C. J., et al. (2001) Methylation of his-tone H4 at arginine 3 occurs in vivo and is mediated by the nuclear receptor coactivator PRMT1. Curr. Biol., 11, 996-1000.
30. Wang, H., Huang, Z. Q., Xia, L., et al. (2001) Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor. Science, 293, 853-857.
31. Yu, Z., Vogel, G., Coulombe, Y., Dubeau, D., Spehalski, E., Hébert, J., Ferguson, D. O., Masson, J. Y. and Richard, S. (2012) The MRE11 GAR motif regulates DNA double-strand break processing and ATR activation. Cell Res., 22, 305-320.
32. Boisvert, F. M., Rhie, A., Richard, S. and Doherty, A. J. (2005) The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity. Cell Cycle, 4, 1834-1841.
33. Bedford, M. T., Frankel, A., Yaffe, M. B., Clarke, S., Leder, P. and Richard, S. (2000) Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains. J. Biol. Chem., 275, 16030-16036.
34. Goulet, I., Gauvin, G., Boisvenue, S. and Côté, J. (2007) Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specifcity, and subcellular localization. J. Biol. Chem., 282, 33009-33021.
35. Yoshimatsu, M., Toyokawa, G., Hayami, S., et al. (2011) Dysregulation of PRMT1 and PRMT6, Type I arginine methyltransferases, is involved in various types of human cancers. Int. J. Cancer, 128, 562-573.
36. Herrmann, F. and Fackelmayer, F. O. (2009) Nucleo-cytoplasmic shuttling of protein arginine methyltransferase 1 (PRMT1) requires enzymatic activity. Genes Cells, 14, 309-317.
37. Baldwin, R. M., Morettin, A., Paris, G., Goulet, I. and Côté, J. (2012) Alternatively spliced protein arginine methyltransferase 1 isoform PRMT1v2 promotes the survival and invasiveness of breast cancer cells. Cell Cycle, 11, 4597-4612.
38. Shtutman, M., Levina, E., Ohouo, P., Baig, M. and Roninson, I. B. (2006) Cell adhesion molecule L1 disrupts E-cadherin-containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells. Cancer Res., 66, 11370-11380.
39. Tomaskovic-Crook, E., Thompson, E. W. and Thiery, J. P. (2009) Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res., 11, 213.
40. Hiscox, S., Jiang, W. G., Obermeier, K., Taylor, K., Morgan, L., Burmi, R., Barrow, D. and Nicholson, R. I. (2006) Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation. Int. J. Cancer, 118, 290-301.
41. Van Aken, E., De Wever, O., Correia da Rocha, A. S. and Mareel, M. (2001) Defective E-cadherin/catenin complexes in human cancer. Virchows Arch., 439, 725-751.
42. Morrogh, M., Andrade, V. P., Giri, D., et al. (2012) Cadherin-catenin complex dissociation in lobular neoplasia of the breast. Breast Cancer Res. Treat., 132, 641-652.
43. Birchmeier, W. and Behrens, J. (1994) Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim. Biophys. Acta, 1198, 11-26.
44. Hart, M., Concordet, J. P., Lassot, I., et al. (1999) The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr. Biol., 9, 207-210.
45. Latres, E., Chiaur, D. S. and Pagano, M. (1999) The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene, 18, 849-854.
46. Winston, J. T., Strack, P., Beer-Romero, P., Chu, C. Y., Elledge, S. J. and Harper, J. W. (1999) The SCFbeta-TRCP-ubiquitin ligase complex associates specifcally with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev., 13, 270-283.
47. Cha, B., Kim, W., Kim, Y. K., et al. (2011) Methylation by protein arginine methyltransferase 1 increases stability of Axin, a negative regulator of Wnt signaling. Oncogene, 30, 2379-2389.
48. Harvey, J. M., Clark, G. M., Osborne, C. K. and Allred, D. C. (1999) Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J. Clin. Oncol., 17, 1474-1481.
49. Le Romancer, M., Treilleux, I., Leconte, N., Robin-Lespinasse, Y., Sen-tis, S., Bouchekioua-Bouzaghou, K., Goddard, S., Gobert-Gosse, S. and Corbo, L. (2008) Regulation of estrogen rapid signaling through arginine methylation by PRMT1. Mol. Cell, 31, 212-221.
50. Le Romancer, M., Treilleux, I., Bouchekioua-Bouzaghou, K., Sentis, S. and Corbo, L. (2010) Methylation, a key step for nongenomic estrogen signaling in breast tumors. Steroids, 75, 560-564.
51. Poulard, C., Treilleux, I., Lavergne, E., Bouchekioua-Bouzaghou, K., God-dard-Léon, S., Chabaud, S., Trédan, O., Corbo, L. and Le Romancer, M. (2012) Activation of rapid oestrogen signalling in aggressive human breast cancers. EMBO Mol. Med., 4, 1200-1213.
52. Ciruelos Gil, E. M. (2014) Targeting the PI3K/AKT/mTOR pathway in estrogen receptor-positive breast cancer. Cancer Treat. Rev., 40, 862-871.
53. Simoncini, T., Hafezi-Moghadam, A., Brazil, D. P., Ley, K., Chin, W. W. and Liao, J. K. (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature, 407, 538-541.
54. Yamagata, K., Daitoku, H., Takahashi, Y., Namiki, K., Hisatake, K., Kako, K., Mukai, H., Kasuya, Y. and Fukamizu, A. (2008) Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt. Mol. Cell, 32, 221-231.
55. Sakamaki, J., Daitoku, H., Ueno, K., Hagiwara, A., Yamagata, K. and Fukamizu, A. (2011) Arginine methylation of BCL-2 antagonist of cell death (BAD) counteracts its phosphorylation and inactivation by Akt. Proc. Natl. Acad. Sci. U. S. A., 108, 6085-6090.
56. Cho, J. H., Lee, M. K., Yoon, K. W., Lee, J., Cho, S. G. and Choi, E. J. (2012) Arginine methylation-dependent regulation of ASK1 signaling by PRMT1. Cell Death Differ., 19, 859-870.
57. Yu, Z., Chen, T., Hébert, J., Li, E. and Richard, S. (2009) A mouse PRMT1 null allele defnes an essential role for arginine methylation in genome maintenance and cell proliferation. Mol. Cell. Biol., 29, 2982-2996.
58. Shattuck-Eidens, D., McClure, M., Simard, J., et al. (1995) A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA, 273, 535-541.
59. Guendel, I., Carpio, L., Pedati, C., Schwartz, A., Teal, C., Kashanchi, F. and Kehn-Hall, K. (2010) Methylation of the tumor suppressor protein, BRCA1, infuences its transcriptional cofactor function. PLoS One, 5, e11379.
60. Boisvert, F. M., Déry, U., Masson, J. Y. and Richard, S. (2005) Arginine methylation of MRE11 by PRMT1 is required for DNA damage checkpoint control. Genes Dev., 19, 671-676.
61. Boisvert, F. M., Hendzel, M. J., Masson, J. Y. and Richard, S. (2005) Meth-ylation of MRE11 regulates its nuclear compartmentalization. Cell Cycle, 4, 981-989.
62. Mitchell, T. R., Glenfeld, K., Jeyanthan, K. and Zhu, X. D. (2009) Arginine methylation regulates telomere length and stability. Mol. Cell. Biol., 29, 4918-4934.
63. An, W., Kim, J. and Roeder, R. G. (2004) Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell, 117, 735-748.
64. Massagué, J. (2008) TGFbeta in Cancer. Cell, 134, 215-230.
65. Ikushima, H. and Miyazono, K. (2012) TGF-β signal transduction spreading to a wider feld: a broad variety of mechanisms for context-dependent effects of TGF-β. Cell Tissue Res., 347, 37-49.
66. Xu, J., Wang, A. H., Oses-Prieto, J., et al. (2013) Arginine Methylation Initiates BMP-Induced Smad Signaling. Mol. Cell, 51, 5-19.
67. ten Dijke, P. and Arthur, H. M. (2007) Extracellular control of TGFbeta signalling in vascular development and disease. Nat. Rev. Mol. Cell Biol., 8, 857-869.
68. Blanco Calvo, M., Bolós Fernández, V., Medina Villaamil, V., Aparicio Gallego, G., Díaz Prado, S. and Grande Pulido, E. (2009) Biology of BMP signalling and cancer. Clin. Transl. Oncol., 11, 126-137.
69. Lin, W. J., Gary, J. D., Yang, M. C., Clarke, S. and Herschman, H. R. (1996) The mammalian immediate-early TIS21 protein and the leukemia-associated BTG1 protein interact with a protein-arginine N-methyltransferase. J. Biol. Chem., 271, 15034-15044.
70. Robin-Lespinasse, Y., Sentis, S., Kolytcheff, C., Rostan, M. C., Corbo, L. and Le Romancer, M. (2007) hCAF1, a new regulator of PRMT1-depend-ent arginine methylation. J. Cell Sci., 120, 638-647.
71. Choi, K. S., Kim, J. Y., Lim, S. K., Choi, Y. W., Kim, Y. H., Kang, S. Y., Park, T. J. and Lim, I. K. (2012) TIS21(/BTG2/PC3) accelerates the repair of DNA double strand breaks by enhancing Mre11 methylation and blocking damage signal transfer to the Chk2(T68)-p53(S20) pathway. DNA Repair (Amst)., 11, 965-975.
72. Prévôt, D., Morel, A. P., Voeltzel, T., Rostan, M. C., Rimokh, R., Magaud, J. P. and Corbo, L. (2001) Relationships of the antiproliferative proteins BTG1 and BTG2 with CAF1, the human homolog of a component of the yeast CCR4 transcriptional complex: involvement in estrogen receptor alpha signaling pathway. J. Biol. Chem., 276, 9640-9648.
73. Sheng, S. H., Zhao, C. M. and Sun, G. G. (2014) BTG1 expression correlates with the pathogenesis and progression of breast carcinomas. Tumour Biol., 35, 3317-3326.
74. Zhu, R., Zou, S. T., Wan, J. M., Li, W., Li, X. L. and Zhu, W. (2013) BTG1 inhibits breast cancer cell growth through induction of cell cycle arrest and apoptosis. Oncol. Rep., 30, 2137-2144.
75. Duriez, C., Falette, N., Audoynaud, C., Moyret-Lalle, C., Bensaad, K., Courtois, S., Wang, Q., Soussi, T. and Puisieux, A. (2002) The human BTG2/TIS21/PC3 gene: genomic structure, transcriptional regulation and evaluation as a candidate tumor suppressor gene. Gene, 282, 207-214.
76. Kawakubo, H., Carey, J. L., Brachtel, E., Gupta, V., Green, J. E., Walden, P. D. and Maheswaran, S. (2004) Expression of the NF-kappaB-responsive gene BTG2 is aberrantly regulated in breast cancer. Oncogene, 23, 8310-8319.
77. Scott, H. S., Antonarakis, S. E., Lalioti, M. D., Rossier, C., Silver, P. A. and Henry, M. F. (1998) Identifcation and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2). Genomics, 48, 330-340.
78. Yoshimoto, T., Boehm, M., Olive, M., Crook, M. F., San, H., Langenickel, T. and Nabel, E. G. (2006) The arginine methyltransferase PRMT2 binds RB and regulates E2F function. Exp. Cell Res., 312, 2040-2053.
79. Ganesh, L., Yoshimoto, T., Moorthy, N. C., Akahata, W., Boehm, M., Nabel, E. G. and Nabel, G. J. (2006) Protein methyltransferase 2 inhibits NF-kappaB function and promotes apoptosis. Mol. Cell. Biol., 26, 3864-3874.
80. Lakowski, T. M. and Frankel, A. (2009) Kinetic analysis of human protein arginine N-methyltransferase 2: formation of monomethyl-and asymmetric dimethyl-arginine residues on histone H4. Biochem. J., 421, 253-261.
81. Blythe, S. A., Cha, S. W., Tadjuidje, E., Heasman, J. and Klein, P. S. (2010) beta-Catenin primes organizer gene expression by recruiting a histone H3 arginine 8 methyltransferase, Prmt2. Dev. Cell, 19, 220-231.
82. Lu, X. L., Cao, X., Liu, X. Y. and Jiao, B. H. (2010) Recent progress of Src SH2 and SH3 inhibitors as anticancer agents. Curr. Med. Chem., 17, 1117-1124.
83. Zhong, J., Cao, R. X., Hong, T., Yang, J., Zu, X. Y., Xiao, X. H., Liu, J. H. and Wen, G. B. (2011) Identifcation and expression analysis of a novel transcript of the human PRMT2 gene resulted from alternative polyade-nylation in breast cancer. Gene, 487, 1-9.
84. Zhong, J., Cao, R. X., Zu, X. Y., et al. (2012) Identifcation and characterization of novel spliced variants of PRMT2 in breast carcinoma. FEBS J., 279, 316-335.
85. Qi, C., Chang, J., Zhu, Y., Yeldandi, A. V., Rao, S. M. and Zhu, Y. J. (2002) Identifcation of protein arginine methyltransferase 2 as a coactivator for estrogen receptor alpha. J. Biol. Chem., 277, 28624-28630.
86. Barrallo-Gimeno, A. and Nieto, M. A. (2005) The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development, 132, 3151-3161.
87. Zhong J., Cao R.X., Liu J.H., Liu Y.B., Wang J., Liu L.P., Chen Y.J., Yang J., Zhang Q.H., Wu Y., Ding W.J., Hong T., Xiao X.H., Zu X.Y. and Wen G.B. (2013) Nuclear loss of protein arginine N-methyltransferase 2 in breast carcinoma is associated with tumor grade and overexpression of cyclin D1 protein. Oncogene, doi: 10.1038/onc.2013.500.
88. Tang, J., Gary, J. D., Clarke, S. and Herschman, H. R. (1998) PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specifcity, and regulation. J. Biol. Chem., 273, 16935-16945.
89. Swiercz, R., Cheng, D., Kim, D. and Bedford, M. T. (2007) Riboso-mal protein rpS2 is hypomethylated in PRMT3-defcient mice. J. Biol. Chem., 282, 16917-16923.
90. Choi, S., Jung, C. R., Kim, J. Y. and Im, D. S. (2008) PRMT3 inhibits ubiquitination of ribosomal protein S2 and together forms an active enzyme complex. Biochim. Biophys. Acta, 1780, 1062-1069.
91. Lai, Y., Song, M., Hakala, K., Weintraub, S. T. and Shiio, Y. (2011) Pro-teomic dissection of the von Hippel-Lindau (VHL) interactome. J. Pro-teome Res., 10, 5175-5182.
92. Heller, G., Geradts, J., Ziegler, B., et al. (2007) Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast Cancer Res. Treat., 103, 283-291.
93. Takahashi, Y., Iwai, M., Kawai, T., et al. (2012) Aberrant expression of tumor suppressors CADM1 and 4.1B in invasive lesions of primary breast cancer. Breast Cancer, 19, 242-252.
94. Singh, V., Miranda, T. B., Jiang, W., et al. (2004) DAL-1/4.1B tumor suppressor interacts with protein arginine N-methyltransferase 3 (PRMT3) and inhibits its ability to methylate substrates in vitro and in vivo. Onco-gene, 23, 7761-7771.
95. Yadav, N., Lee, J., Kim, J., Shen, J., Hu, M. C., Aldaz, C. M. and Bedford, M. T. (2003) Specifc protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-defcient mice. Proc. Natl. Acad. Sci. U. S. A., 100, 6464-6468.
96. Yadav, N., Cheng, D., Richard, S., Morel, M., Iyer, V. R., Aldaz, C. M. and Bedford, M. T. (2008) CARM1 promotes adipocyte differentiation by coactivating PPARgamma. EMBO Rep., 9, 193-198.
97. O'Brien, K. B., Alberich-Jordà, M., Yadav, N., et al. (2010) CARM1 is required for proper control of proliferation and differentiation of pulmonary epithelial cells. Development, 137, 2147-2156.
98. Kim, J., Lee, J., Yadav, N., Wu, Q., Carter, C., Richard, S., Richie, E. and Bedford, M. T. (2004) Loss of CARM1 results in hypomethylation of thymocyte cyclic AMP-regulated phosphoprotein and deregulated early T cell development. J. Biol. Chem., 279, 25339-25344.
99. Ito, T., Yadav, N., Lee, J., et al. (2009) Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossifcation. BMC Dev. Biol., 9, 47.
100. Kim, D., Lee, J., Cheng, D., Li, J., Carter, C., Richie, E. and Bedford, M. T. (2010) Enzymatic activity is required for the in vivo functions of CARM1. J. Biol. Chem., 285, 1147-1152.
101. Kawabe, Y., Wang, Y. X., McKinnell, I. W., Bedford, M. T. and Rudnicki, M. A. (2012) Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during asymmetric satellite stem cell divisions. Cell Stem Cell, 11, 333-345.
102. Dacwag, C. S., Bedford, M. T., Sif, S. and Imbalzano, A. N. (2009) Distinct protein arginine methyltransferases promote ATP-dependent chro-matin remodeling function at different stages of skeletal muscle differentiation. Mol. Cell. Biol., 29, 1909-1921.
103. Chen, D., Ma, H., Hong, H., Koh, S. S., Huang, S. M., Schurter, B. T., Aswad, D. W. and Stallcup, M. R. (1999) Regulation of transcription by a protein methyltransferase. Science, 284, 2174-2177.
104. Ohkura, N., Takahashi, M., Yaguchi, H., Nagamura, Y. and Tsukada, T. (2005) Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA splicing in an isoform-specifc manner. J. Biol. Chem., 280, 28927-28935.
105. El Messaoudi, S., Fabbrizio, E., Rodriguez, C., et al. (2006) Coactivator-associated arginine methyltransferase 1 (CARM1) is a positive regulator of the Cyclin E1 gene. Proc. Natl. Acad. Sci. U. S. A., 103, 13351-13356.
106. Lee, Y. H., Bedford, M. T. and Stallcup, M. R. (2011) Regulated recruitment of tumor suppressor BRCA1 to the p21 gene by coactivator meth-ylation. Genes Dev., 25, 176-188.
107. Lee, Y. H. and Stallcup, M. R. (2011) Roles of protein arginine meth-ylation in DNA damage signaling pathways is CARM1 a life-or-death decision point? Cell Cycle, 10, 1343-1344.
108. Lupien, M., Eeckhoute, J., Meyer, C. A., Krum, S. A., Rhodes, D. R., Liu, X. S. and Brown, M. (2009) Coactivator function defnes the active estrogen receptor alpha cistrome. Mol. Cell. Biol., 29, 3413-3423.
109. Schurter, B. T., Koh, S. S., Chen, D., et al. (2001) Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry, 40, 5747-5756.
110. Zhao, H. Y., Zhang, Y. J., Dai, H., Zhang, Y. and Shen, Y. F. (2011) CARM1 mediates modulation of Sox2. PLoS One, 6, e27026.
111. Ceschin, D. G., Walia, M., Wenk, S. S., et al. (2011) Methylation specifes distinct estrogen-induced binding site repertoires of CBP to chromatin. Genes Dev., 25, 1132-1146.
112. Naeem, H., Cheng, D., Zhao, Q., Underhill, C., Tini, M., Bedford, M. T. and Torchia, J. (2007) The activity and stability of the transcriptional coactivator p/CIP/SRC-3 are regulated by CARM1-dependent methyla-tion. Mol. Cell. Biol., 27, 120-134.
113. Feng, Q., Yi, P., Wong, J. and O'Malley, B. W. (2006) Signaling within a coactivator complex: methylation of SRC-3/AIB1 is a molecular switch for complex disassembly. Mol. Cell. Biol., 26, 7846-7857.
114. Chevillard-Briet, M., Trouche, D. and Vandel, L. (2002) Control of CBP co-activating activity by arginine methylation. EMBO J., 21, 5457-5466.
115. Sims, R. J. 3rd, Rojas, L. A., Beck, D., Bonasio, R., Schüller, R., Drury, W. J. 3rd, Eick, D. and Reinberg, D. (2011) The C-terminal domain of RNA polymerase II is modifed by site-specifc methylation. Science, 332, 99-103.
116. Carascossa, S., Dudek, P., Cenni, B., Briand, P. A. and Picard, D. (2010) CARM1 mediates the ligand-independent and tamoxifen-resistant activation of the estrogen receptor alpha by cAMP. Genes Dev., 24, 708-719.
117. Kuhn, P., Chumanov, R., Wang, Y., Ge, Y., Burgess, R. R. and Xu, W. (2011) Automethylation of CARM1 allows coupling of transcription and mRNA splicing. Nucleic Acids Res., 39, 2717-2726.
118. Frietze, S., Lupien, M., Silver, P. A. and Brown, M. (2008) CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1. Cancer Res., 68, 301-306.
119. Mann, M., Cortez, V. and Vadlamudi, R. (2013) PELP1 oncogenic functions involve CARM1 regulation. Carcinogenesis, 34, 1468-1475.
120. Vadlamudi, R. K., Manavathi, B., Balasenthil, S., Nair, S. S., Yang, Z., Sahin, A. A. and Kumar, R. (2005) Functional implications of altered subcellular localization of PELP1 in breast cancer cells. Cancer Res., 65, 7724-7732.
121. Gururaj, A. E., Peng, S., Vadlamudi, R. K. and Kumar, R. (2007) Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha coactivator, through proline-, glutamic acid-, and leucine-rich protein-1 (PELP1). Mol. Endocrinol., 21, 1847-1860.
122. Rajhans, R., Nair, S., Holden, A. H., Kumar, R., Tekmal, R. R. and Vadlamudi, R. K. (2007) Oncogenic potential of the nuclear receptor coregulator proline-, glutamic acid-, leucine-rich protein 1/modulator of the nongenomic actions of the estrogen receptor. Cancer Res., 67, 5505-5512.
123. Habashy, H. O., Powe, D. G., Rakha, E. A., Ball, G., Macmillan, R. D., Green, A. R. and Ellis, I. O. (2010) The prognostic signifcance of PELP1 expression in invasive breast cancer with emphasis on the ER-positive luminal-like subtype. Breast Cancer Res. Treat., 120, 603-612.
124. Roy, S., Chakravarty, D., Cortez, V., et al. (2012) Signifcance of PELP1 in ER-negative breast cancer metastasis. Mol. Cancer Res., 10, 25-33.
125. Cheng, H., Qin, Y., Fan, H., Su, P., Zhang, X., Zhang, H. and Zhou, G. (2013) Overexpression of CARM1 in breast cancer is correlated with poorly characterized clinicopathologic parameters and molecular subtypes. Diagn. Pathol., 8, 129.
126. Habashy, H. O., Rakha, E. A., Ellis, I. O. and Powe, D. G. (2013) The oestrogen receptor coactivator CARM1 has an oncogenic effect and is associated with poor prognosis in breast cancer. Breast Cancer Res. Treat., 140, 307-316.
127. Davis, M. B., Liu, X., Wang, S., Reeves, J., Khramtsov, A., Huo, D. and Olopade, O. I. (2013) Expression and sub-cellular localization of an epi-genetic regulator, co-activator arginine methyltransferase 1 (CARM1), is associated with specifc breast cancer subtypes and ethnicity. Mol. Cancer, 12, 40.
128. Lee, D. Y., Northrop, J. P., Kuo, M. H. and Stallcup, M. R. (2006) His-tone H3 lysine 9 methyltransferase G9a is a transcriptional coactivator for nuclear receptors. J. Biol. Chem., 281, 8476-8485.
129. Al-Dhaheri, M., Wu, J., Skliris, G. P., et al. (2011) CARM1 is an important determinant of ERα-dependent breast cancer cell differentiation and proliferation in breast cancer cells. Cancer Res., 71, 2118-2128.
130. Wang, L., Zhao, Z., Meyer, M. B., et al. (2014) CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis. Cancer Cell, 25, 21-36.
131. Herrmann, F., Pably, P., Eckerich, C., Bedford, M. T. and Fackelmayer, F. O. (2009) Human protein arginine methyltransferases in vivo-distinct properties of eight canonical members of the PRMT family. J. Cell Sci., 122, 667-677.
132. Tee, W. W., Pardo, M., Theunissen, T. W., Yu, L., Choudhary, J. S., Hajkova, P. and Surani, M. A. (2010) Prmt5 is essential for early mouse development and acts in the cytoplasm to maintain ES cell pluripotency. Genes Dev., 24, 2772-2777.
133. Fabbrizio, E., El Messaoudi, S., Polanowska, J., et al. (2002) Negative regulation of transcription by the type II arginine methyltransferase PRMT5. EMBO Rep., 3, 641-645.
134. Deng, X., Gu, L., Liu, C., et al. (2010) Arginine methylation mediated by the Arabidopsis homolog of PRMT5 is essential for proper pre-mRNA splicing. Proc. Natl. Acad. Sci. U. S. A., 107, 19114-19119.
135. Sanchez, S. E., Petrillo, E., Beckwith, E. J., et al. (2010) A methyl trans-ferase links the circadian clock to the regulation of alternative splicing. Nature, 468, 112-116.
136. Bezzi, M., Teo, S. X., Muller, J., Mok, W. C., Sahu, S. K., Vardy, L. A., Bonday, Z. Q. and Guccione, E. (2013) Regulation of constitutive and alternative splicing by PRMT5 reveals a role for Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery. Genes Dev., 27, 1903-1916.
137. Jansson, M., Durant, S. T., Cho, E. C., Sheahan, S., Edelmann, M., Kes-sler, B. and La Thangue, N. B. (2008) Arginine methylation regulates the p53 response. Nat. Cell Biol., 10, 1431-1439.
138. Andreu-Pérez, P., Esteve-Puig, R., de Torre-Minguela, C., et al. (2011) Protein arginine methyltransferase 5 regulates ERK1/2 signal transduc-tion amplitude and cell fate through CRAF. Sci. Signal., 4, ra58.
139. Hsu, J. M., Chen, C. T., Chou, C. K., et al. (2011) Crosstalk between Arg 1175 methylation and Tyr 1173 phosphorylation negatively modulates EGFR-mediated ERK activation. Nat. Cell Biol., 13, 174-181.
140. Cho, E. C., Zheng, S., Munro, S., et al. (2012) Arginine methylation controls growth regulation by E2F-1. EMBO J., 31, 1785-1797.
141. Ren, J., Wang, Y., Liang, Y., Zhang, Y., Bao, S. and Xu, Z. (2010) Meth-ylation of ribosomal protein S10 by protein-arginine methyltransferase 5 regulates ribosome biogenesis. J. Biol. Chem., 285, 12695-12705.
142. Zhou, Z., Sun, X., Zou, Z., et al. (2010) PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130. Cell Res., 20, 1023-1033.
143. Dacwag, C. S., Ohkawa, Y., Pal, S., Sif, S. and Imbalzano, A. N. (2007) The protein arginine methyltransferase Prmt5 is required for myogenesis because it facilitates ATP-dependent chromatin remodeling. Mol. Cell. Biol., 27, 384-394.
144. Mallappa, C., Hu, Y. J., Shamulailatpam, P., Tae, S., Sif, S. and Imbalzano, A. N. (2011) The expression of myogenic microRNAs indirectly requires protein arginine methyltransferase (Prmt)5 but directly requires Prmt4. Nucleic Acids Res., 39, 1243-1255.
145. Ancelin, K., Lange, U. C., Hajkova, P., Schneider, R., Bannister, A. J., Kouzarides, T. and Surani, M. A. (2006) Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat. Cell Biol., 8, 623-630.
146. Eckert, D., Biermann, K., Nettersheim, D., Gillis, A. J., Steger, K., Jäck, H. M., Müller, A. M., Looijenga, L. H. and Schorle, H. (2008) Expression of BLIMP1/PRMT5 and concurrent histone H2A/H4 arginine 3 dimeth-ylation in fetal germ cells, CIS/IGCNU and germ cell tumors. BMC Dev. Biol., 8, 106.
147. Powers, M. A., Fay, M. M., Factor, R. E., Welm, A. L. and Ullman, K. S. (2011) Protein arginine methyltransferase 5 accelerates tumor growth by arginine methylation of the tumor suppressor programmed cell death 4. Cancer Res., 71, 5579-5587.
148. Wen, Y. H., Shi, X., Chiriboga, L., Matsahashi, S., Yee, H. and Afonja, O. (2007) Alterations in the expression of PDCD4 in ductal carcinoma of the breast. Oncol. Rep., 18, 1387-1393.
149. Yang, H. S., Knies, J. L., Stark, C. and Colburn, N. H. (2003) Pdcd4 suppresses tumor phenotype in JB6 cells by inhibiting AP-1 transactivation. Oncogene, 22, 3712-3720.
150. Jiang, W., Roemer, M. E. and Newsham, I. F. (2005) The tumor suppressor DAL-1/4.1B modulates protein arginine N-methyltransferase 5 activity in a substrate-specifc manner. Biochem. Biophys. Res. Com-mun., 329, 522-530.
151. Jiang, W. and Newsham, I. F. (2006) The tumor suppressor DAL-1/4.1B and protein methylation cooperate in inducing apoptosis in MCF-7 breast cancer cells. Mol. Cancer, 5, 4.
152. Singhroy, D. N., Mesplède, T., Sabbah, A., Quashie, P. K., Falgueyret, J. P. and Wainberg, M. A. (2013) Automethylation of protein arginine methyltransferase 6 (PRMT6) regulates its stability and its anti-HIV-1 activity. Retrovirology, 10, 73.
153. Neault, M., Mallette, F. A., Vogel, G., Michaud-Levesque, J. and Richard, S. (2012) Ablation of PRMT6 reveals a role as a negative transcrip-tional regulator of the p53 tumor suppressor. Nucleic Acids Res., 40, 9513-9521.
154. Hyllus, D., Stein, C., Schnabel, K., Schiltz, E., Imhof, A., Dou, Y., Hsieh, J. and Bauer, U. M. (2007) PRMT6-mediated methylation of R2 in his-tone H3 antagonizes H3 K4 trimethylation. Genes Dev., 21, 3369-3380.
155. Michaud-Levesque, J. and Richard, S. (2009) Thrombospondin-1 is a transcriptional repression target of PRMT6. J. Biol. Chem., 284, 21338-21346.
156. Herglotz, J., Kuvardina, O. N., Kolodziej, S., Kumar, A., Hussong, H., Grez, M. and Lausen, J. (2013) Histone arginine methylation keeps RUNX1 target genes in an intermediate state. Oncogene, 32, 2565-2575.
157. Phalke, S., Mzoughi, S., Bezzi, M., et al. (2012) p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6. Nucleic Acids Res., 40, 9534-9542.
158. Casadio, F., Lu, X., Pollock, S. B., LeRoy, G., Garcia, B. A., Muir, T. W., Roeder, R. G. and Allis, C. D. (2013) H3R42me2a is a histone modifca-tion with positive transcriptional effects. Proc. Natl. Acad. Sci. U. S. A., 110, 14894-14899.
159. Waldmann, T., Izzo, A., Kamieniarz, K., et al. (2011) Methylation of H2AR29 is a novel repressive PRMT6 target. Epigenetics Chromatin, 4, 11.
160. Dowhan, D. H., Harrison, M. J., Eriksson, N. A., et al. (2012) Protein arginine methyltransferase 6-dependent gene expression and splicing: association with breast cancer outcomes. Endocr. Relat. Cancer, 19, 509-526.
161. Kim, N. H., Kim, S. N., Seo, D. W., Han, J. W. and Kim, Y. K. (2013) PRMT6 overexpression upregulates TSP-1 and downregulates MMPs: its implication in motility and invasion. Biochem. Biophys. Res. Com-mun., 432, 60-65.
162. Chu, M. C., Selam, F. B. and Taylor, H. S. (2004) HOXA10 regulates p53 expression and matrigel invasion in human breast cancer cells. Cancer Biol. Ther., 3, 568-572.
163. Somiari, S. B., Somiari, R. I., Heckman, C. M., Olsen, C. H., Jordan, R. M., Russell, S. J. and Shriver, C. D. (2006) Circulating MMP2 and MMP9 in breast cancer-potential role in classifcation of patients into low risk, high risk, benign disease and breast cancer categories. Int. J. Cancer, 119, 1403-1411.
164. Somiari, S. B., Shriver, C. D., Heckman, C., et al. (2006) Plasma concentration and activity of matrix metalloproteinase 2 and 9 in patients with breast disease, breast cancer and at risk of developing breast cancer. Cancer Lett., 233, 98-107.
165. Qin, L., Liao, L., Redmond, A., Young, L., Yuan, Y., Chen, H., O'Malley, B. W. and Xu, J. (2008) The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression. Mol. Cell. Biol., 28, 5937-5950.
166. Wang, X., Lu, H., Urvalek, A. M., Li, T., Yu, L., Lamar, J., DiPersio, C. M., Feustel, P. J. and Zhao, J. (2011) KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene, 30, 1901-1911.
167. Liu, Y., Xin, T., Jiang, Q. Y., et al. (2013) CD147, MMP9 expression and clinical signifcance of basal-like breast cancer. Med. Oncol., 30, 366.
168. Prasad, C. P., Chaurasiya, S. K., Axelsson, L. and Andersson, T. (2013) WNT-5A triggers Cdc42 activation leading to an ERK1/2 dependent decrease in MMP9 activity and invasive migration of breast cancer cells. Mol. Oncol., 7, 870-883.
169. Harrison, M. J., Tang, Y. H. and Dowhan, D. H. (2010) Protein argi-nine methyltransferase 6 regulates multiple aspects of gene expression. Nucleic Acids Res., 38, 2201-2216.
170. Miranda, T. B., Webb, K. J., Edberg, D. D., Reeves, R. and Clarke, S. (2005) Protein arginine methyltransferase 6 specifcally methylates the nonhistone chromatin protein HMGA1a. Biochem. Biophys. Res. Com-mun., 336, 831-835.
171. Zou, Y., Webb, K., Perna, A. D., Zhang, Q., Clarke, S. and Wang, Y. (2007) A mass spectrometric study on the in vitro methylation of HMGA1a and HMGA1b proteins by PRMTs: methylation specifcity, the effect of binding to AT-rich duplex DNA, and the effect of C-termi-nal phosphorylation. Biochemistry, 46, 7896-7906.
172. Liu, F., Chau, K. Y., Arlotta, P. and Ono, S. J. (2001) The HMG I proteins: dynamic roles in gene activation, development, and tumorigenesis. Immunol. Res., 24, 13-29.
173. Reeves, R. and Beckerbauer, L. (2001) HMGI/Y proteins: fexible regulators of transcription and chromatin structure. Biochim. Biophys. Acta, 1519, 13-29.
174. Dolde, C. E., Mukherjee, M., Cho, C. and Resar, L. M. (2002) HMG-I/Y in human breast cancer cell lines. Breast Cancer Res. Treat., 71, 181-191.
175. Flohr, A. M., Rogalla, P., Bonk, U., et al. (2003) High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade. Histol. Histopathol., 18, 999-1004.
176. Chiappetta, G., Botti, G., Monaco, M., et al. (2004) HMGA1 protein overexpression in human breast carcinomas: correlation with ErbB2 expression. Clin. Cancer Res., 10, 7637-7644.
177. Chiappetta, G., Ottaiano, A., Vuttariello, E., et al. (2010) HMGA1 protein expression in familial breast carcinoma patients. Eur. J. Cancer, 46, 332-339.
178. Treff, N. R., Pouchnik, D., Dement, G. A., Britt, R. L. and Reeves, R. (2004) High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells. Oncogene, 23, 777-785.
179. Stimpf, M., Tong, D., Fasching, B., Schuster, E., Obermair, A., Leodolter, S. and Zeillinger, R. (2002) Vascular endothelial growth factor splice variants and their prognostic value in breast and ovarian cancer. Clin. Cancer Res., 8, 2253-2259.
180. Wang, L., Duke, L., Zhang, P. S., Arlinghaus, R. B., Symmans, W. F., Sahin, A., Mendez, R. and Dai, J. L. (2003) Alternative splicing disrupts a nuclear localization signal in spleen tyrosine kinase that is required for invasion suppression in breast cancer. Cancer Res., 63, 4724-4730.
181. Albertella, M. R., Lau, A. and O'Connor, M. J. (2005) The overexpres-sion of specialized DNA polymerases in cancer. DNA Repair (Amst)., 4, 583-593.
182. Abdel-Fatah, T. M., Russell, R., Agarwal, D., et al. (2014) DNA poly-merase β defciency is linked to aggressive breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts. Mol. Oncol., 8, 520-532.
183. Newman, L., Xia, W., Yang, H. Y., Sahin, A., Bondy, M., Lukmanji, F., Hung, M. C. and Lee, M. H. (2001) Correlation of p27 protein expression with HER-2/neu expression in breast cancer. Mol. Carcinog., 30, 169-175.
184. Bearss, D. J., Lee, R. J., Troyer, D. A., Pestell, R. G. and Windle, J. J. (2002) Differential effects of p21(WAF1/CIP1) defciency on MMTV-ras and MMTV-myc mammary tumor properties. Cancer Res., 62, 2077-2084.
185. Spataro, V. J., Litman, H., Viale, G., et al.; International Breast Cancer Study Group. (2003) Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with beneft from one course of perioperative chemotherapy in patients with negative lymph node status: results from International Breast Cancer Study Group Trial V. Cancer, 97, 1591-1600.
186. Alkarain, A., Jordan, R. and Slingerland, J. (2004) p27 deregulation in breast cancer: prognostic signifcance and implications for therapy. J. Mammary Gland Biol. Neoplasia, 9, 67-80.
187. Crawford, Y. G., Gauthier, M. L., Joubel, A., Mantei, K., Kozakiewicz, K., Afshari, C. A. and Tlsty, T. D. (2004) Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program. Cancer Cell, 5, 263-273.
188. Stein, C., Riedl, S., Rüthnick, D., Nötzold, R. R. and Bauer, U. M. (2012) The arginine methyltransferase PRMT6 regulates cell proliferation and senescence through transcriptional repression of tumor suppressor genes. Nucleic Acids Res., 40, 9522-9533.
189. Kleinschmidt, M. A., de Graaf, P., van Teeffelen, H. A. and Timmers, H. T. (2012) Cell cycle regulation by the PRMT6 arginine methyltrans-ferase through repression of cyclin-dependent kinase inhibitors. PLoS One, 7, e41446.
190. Wang, X., Huang, Y., Zhao, J., Zhang, Y., Lu, J. and Huang, B. (2012) Suppression of PRMT6-mediated arginine methylation of p16 protein potentiates its ability to arrest A549 cell proliferation. Int. J. Biochem. Cell Biol., 44, 2333-2341.
191. Miranda, T. B., Miranda, M., Frankel, A. and Clarke, S. (2004) PRMT7 is a member of the protein arginine methyltransferase family with a distinct substrate specifcity. J. Biol. Chem., 279, 22902-22907.
192. Hasegawa, M., Toma-Fukai, S., Kim, J. D., Fukamizu, A. and Shimizu, T. (2014) Protein arginine methyltransferase 7 has a novel homodimer-like structure formed by tandem repeats. FEBS Lett., 588, 1942-1948.
193. Lee, J. H., Cook, J. R., Yang, Z. H., Mirochnitchenko, O., Gunderson, S. I., Felix, A. M., Herth, N., Hoffmann, R. and Pestka, S. (2005) PRMT7, a new protein arginine methyltransferase that synthesizes symmetric dimethylarginine. J. Biol. Chem., 280, 3656-3664.
194. Karkhanis, V., Wang, L., Tae, S., Hu, Y. J., Imbalzano, A. N. and Sif, S. (2012) Protein arginine methyltransferase 7 regulates cellular response to DNA damage by methylating promoter histones H2A and H4 of the polymerase δ catalytic subunit gene, POLD1. J. Biol. Chem., 287, 29801-29814.
195. Thomassen, M., Tan, Q. and Kruse, T. A. (2009) Gene expression meta-analysis identifes chromosomal regions and candidate genes involved in breast cancer metastasis. Breast Cancer Res. Treat., 113, 239-249.
196. Jelinic, P., Stehle, J. C. and Shaw, P. (2006) The testis-specifc factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation. PLoS Biol., 4, e355.
197. Martin-Kleiner, I. (2012) BORIS in human cancers-a review. Eur. J. Cancer, 48, 929-935.
198. Yost, J. M., Korboukh, I., Liu, F., Gao, C. and Jin, J. (2011) Targets in epigenetics: inhibiting the methyl writers of the histone code. Curr. Chem. Genomics, 5, 72-84.
199. Vhuiyan, M., Thomas, D., Hossen, F. and Frankel, A. (2013) Targeting protein arginine N-methyltransferases with peptide-based inhibitors: opportunities and challenges. Future Med. Chem., 5, 2199-2206.
200. Cheng, D., Yadav, N., King, R. W., Swanson, M. S., Weinstein, E. J. and Bedford, M. T. (2004) Small molecule regulators of protein arginine methyltransferases. J. Biol. Chem., 279, 23892-23899.
201. Ragno, R., Simeoni, S., Castellano, S., et al. (2007) Small molecule inhibitors of histone arginine methyltransferases: homology modeling, molecular docking, binding mode analysis, and biological evaluations. J. Med. Chem., 50, 1241-1253.
202. Bonham, K., Hemmers, S., Lim, Y. H., Hill, D. M., Finn, M. G. and Mowen, K. A. (2010) Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production. FEBS J., 277, 2096-2108.
203. Purandare, A. V., Chen, Z., Huynh, T., et al. (2008) Pyrazole inhibitors of coactivator associated arginine methyltransferase 1 (CARM1). Bioorg. Med. Chem. Lett., 18, 4438-4441.
204. Therrien, E., Larouche, G., Manku, S., et al. (2009) 1, 2-Diamines as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1). Bioorg. Med. Chem. Lett., 19, 6725-6732.
205. Spannhoff, A., Heinke, R., Bauer, I., et al. (2007) Target-based approach to inhibitors of histone arginine methyltransferases. J. Med. Chem., 50, 2319-2325.
206. Bissinger, E. M., Heinke, R., Spannhoff, A., et al. (2011) Acyl derivatives of p-aminosulfonamides and dapsone as new inhibitors of the arginine methyltransferase hPRMT1. Bioorg. Med. Chem., 19, 3717-3731.
207. Wang, J., Chen, L., Sinha, S. H., et al. (2012) Pharmacophore-based virtual screening and biological evaluation of small molecule inhibitors for protein arginine methylation. J. Med. Chem., 55, 7978-7987.
208. Yan, L., Yan, C., Qian, K., et al. (2014) Diamidine compounds for selective inhibition of protein arginine methyltransferase 1. J. Med. Chem., 57, 2611-2622.
209. Cheng, D. and Bedford, M. T. (2011) Xenoestrogens regulate the activity of arginine methyltransferases. Chembiochem, 12, 323-329.