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Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1
Cell Biology
Volume 1, Issue 2, July 2013, Pages: 18-23
Received: Oct. 3, 2013; Published: Dec. 10, 2013
Volume 1, Issue 2, July 2013, Pages: 18-23
Received: Oct. 3, 2013; Published: Dec. 10, 2013
Views 4115 Downloads 134
Authors
Kenta Fujimoto, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan
Shigeki Arai, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan
Maki Matsubara, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan
Kun Du, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan
Yasuto Araki, Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan
Akio Matsushita, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan; Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan
Riki Kurokawa, Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan
Abstract
Chromosomal translocation product, TLS-CHOP (Translocated in liposarcoma-CCAAT/enhancer binding protein homologous protein, also named as FUS-DDIT3), has been thought to be a primary cause of myxoid liposarcoma, but the precise molecular function of TLS-CHOP for oncogenesis still remains to be elucidated. Previously we demonstrated that TLS/FUS interacts with protein arginine methyltransferase 1 (PRMT1), and carboxyl-terminal region of TLS is dimethylated by PRMT1. However, it has been uncovered whether TLS-CHOP function is regulated by PRMT1, and is methylated. Here we indicate that TLS-CHOP is not associated with PRMT1 and less methylated even though TLS-CHOP still possesses several potential arginine methylation sites of TLS. Moreover, we established a stable cell line expressing TLS-CHOP as a model system for studying the molecular function of TLS-CHOP. The TLS-CHOP expressing 293T cells exhibited slight growth retardation and decreased level of integrin 51 protein, a fibronectin receptor. It would be possible that the expression of oncoprotein TLS-CHOP might dysregulate arginine-specific methylation elicited via PRMT1 interacting with methylated TLS.
Keywords
TLS-CHOP, FUS-DDIT3, PRMT1, Arginine Methylation, Liposarcoma
To cite this article
Kenta Fujimoto,
Shigeki Arai,
Maki Matsubara,
Kun Du,
Yasuto Araki,
Akio Matsushita,
Riki Kurokawa,
Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1, Cell Biology.
Vol. 1, No. 2,
2013, pp. 18-23.
doi: 10.11648/j.cb.20130102.11
References
[1]
Crozat, A., Aman, P., Mandahl, N. and Ron, D. (1993). Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363, 640-644.
[2]
Rabbitts, T.H., Forster, A., Larson, R. and Nathan, P. (1993). Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet 4, 175-180.
[3]
Antonescu, C.R. et al. (2001). Prognostic impact of P53 status, TLS-CHOP fusion transcript structure, and histological grade in myxoid liposarcoma: a molecular and clinicopathologic study of 82 cases. Clin Cancer Res 7, 3977-3987.
[4]
Zinszner, H., Albalat, R. and Ron, D. (1994). A novel effector domain from the RNA-binding protein TLS or EWS is required for oncogenic transformation by CHOP. Genes Dev 8, 2513-2526.
[5]
Kuroda, M., Ishida, T., Takanashi, M., Satoh, M., Machinami, R. and Watanabe, T. (1997). Oncogenic transformation and inhibition of adipocytic conversion of preadipocytes by TLS/FUS-CHOP type II chimeric protein. Am J Pathol 151, 735-744.
[6]
Pérez-Losada, J. et al. (2000). The chimeric FUS/TLS-CHOP fusion protein specifically induces liposarcomas in transgenic mice. Oncogene 19, 2413-2422.
[7]
Wang, X. et al. (2008). Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454, 126-130.
[8]
Du, K., Arai, S., Kawamura, T., Matsushita, A. and Kurokawa, R. (2011). TLS and PRMT1 synergistically coactivate transcription at the survivin promoter through TLS arginine methylation. Biochem Biophys Res Commun 404, 991-996.
[9]
Hallier, M., Lerga, A., Barnache, S., Tavitian, A. and Moreau-Gachelin, F. (1998). The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS. J Biol Chem 273, 4838-4842.
[10]
Kino, Y., Washizu, C., Aquilanti, E., Okuno, M., Kurosawa, M., Yamada, M., Doi, H. and Nukina, N. (2011). Intracellular localization and splicing regulation of FUS/TLS are variably affected by amyotrophic lateral sclerosis-linked mutations. Nucleic Acids Res 39, 2781-2798.
[11]
Kuroda, M. et al. (2000). Male sterility and enhanced radiation sensitivity in TLS(-/-) mice. EMBO J 19, 453-462.
[12]
Hicks, G.G. et al. (2000). Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nat Genet 24, 175-179.
[13]
Kwiatkowski, T.J. et al. (2009). Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323, 1205-1208.
[14]
Vance, C. et al. (2009). Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323, 1208-1211.
[15]
Tradewell, M.L., Yu, Z., Tibshirani, M., Boulanger, M.C., Durham, H.D. and Richard, S. (2012). Arginine methylation by PRMT1 regulates nuclear-cytoplasmic localization and toxicity of FUS/TLS harbouring ALS-linked mutations. Hum Mol Genet 21, 136-149.
[16]
Zinszner, H., Kuroda, M., Wang, X., Batchvarova, N., Lightfoot, R.T., Remotti, H., Stevens, J.L. and Ron, D. (1998). CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12, 982-995.
[17]
Rapp, T.B., Yang, L., Conrad, E.U., Mandahl, N. and Chansky, H.A. (2002). RNA splicing mediated by YB-1 is inhibited by TLS/CHOP in human myxoid liposarcoma cells. J Orthop Res 20, 723-729.
[18]
Law, W.J., Cann, K.L. and Hicks, G.G. (2006). TLS, EWS and TAF15: a model for transcriptional integration of gene expression. Brief Funct Genomic Proteomic 5, 8-14.
[19]
Kovar, H. (2011). Dr. Jekyll and Mr. Hyde: The Two Faces of the FUS/EWS/TAF15 Protein Family. Sarcoma 2011, 837474.
[20]
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.
[21]
Robin-Lespinasse, Y., Sentis, S., Kolytcheff, C., Rostan, M.C., Corbo, L. and Le Romancer, M. (2007). hCAF1, a new regulator of PRMT1-dependent arginine methylation. J Cell Sci 120, 638-647.
[22]
Vezzalini, M. et al. (2010). Immunohistochemical detection of arginine methylated proteins (MeRP) in archival tissues. Histopathology 57, 725-733.
[23]
Nicholson, T.B., Chen, T. and Richard, S. (2009). The physiological and pathophysiological role of PRMT1-mediated protein arginine methylation. Pharmacol Res 60, 466-474.
[24]
Liu, F. et al. (2011). JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell 19, 283-294.
[25]
Plantefaber, L.C. and Hynes, R.O. (1989). Changes in integrin receptors on oncogenically transformed cells. Cell 56, 281-290.
[26]
Riggi, N., Cironi, L., Provero, P., Suvà, M.L., Stehle, J.C., Baumer, K., Guillou, L. and Stamenkovic, I. (2006). Expression of the FUS-CHOP fusion protein in primary mesenchymal progenitor cells gives rise to a model of myxoid liposarcoma. Cancer Res 66, 7016-7023.
[27]
Thelin-Järnum, S., Göransson, M., Burguete, A.S., Olofsson, A. and Aman, P. (2002). The myxoid liposarcoma specific TLS-CHOP fusion protein localizes to nuclear structures distinct from PML nuclear bodies. Int J Cancer 97, 446-450.
[28]
Bento, C., Andersson, M.K. and Aman, P. (2009). DDIT3/CHOP and the sarcoma fusion oncoprotein FUS-DDIT3/TLS-CHOP bind cyclin-dependent kinase 2. BMC Cell Biol 10, 89.
[29]
Yoshimatsu, M. 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.
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