| Peer-Reviewed

Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1

Received: 3 October 2013     Published: 10 December 2013
Views:       Downloads:
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 51 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.

Published in Cell Biology (Volume 1, Issue 2)
DOI 10.11648/j.cb.20130102.11
Page(s) 18-23
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2013. Published by Science Publishing Group

Keywords

TLS-CHOP, FUS-DDIT3, PRMT1, Arginine Methylation, Liposarcoma

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.
Cite This Article
  • APA Style

    Kenta Fujimoto, Shigeki Arai, Maki Matsubara, Kun Du, Yasuto Araki, et al. (2013). Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1. Cell Biology, 1(2), 18-23. https://doi.org/10.11648/j.cb.20130102.11

    Copy | Download

    ACS Style

    Kenta Fujimoto; Shigeki Arai; Maki Matsubara; Kun Du; Yasuto Araki, et al. Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1. Cell Biol. 2013, 1(2), 18-23. doi: 10.11648/j.cb.20130102.11

    Copy | Download

    AMA Style

    Kenta Fujimoto, Shigeki Arai, Maki Matsubara, Kun Du, Yasuto Araki, et al. Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1. Cell Biol. 2013;1(2):18-23. doi: 10.11648/j.cb.20130102.11

    Copy | Download

  • @article{10.11648/j.cb.20130102.11,
      author = {Kenta Fujimoto and Shigeki Arai and Maki Matsubara and Kun Du and Yasuto Araki and Akio Matsushita and Riki Kurokawa},
      title = {Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1},
      journal = {Cell Biology},
      volume = {1},
      number = {2},
      pages = {18-23},
      doi = {10.11648/j.cb.20130102.11},
      url = {https://doi.org/10.11648/j.cb.20130102.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.cb.20130102.11},
      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 51 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.},
     year = {2013}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Implicated Role of Liposarcoma Related Fusion Oncoprotein TLS-CHOP in the Dysregulation of Arginine-Specific Methylation through PRMT1
    AU  - Kenta Fujimoto
    AU  - Shigeki Arai
    AU  - Maki Matsubara
    AU  - Kun Du
    AU  - Yasuto Araki
    AU  - Akio Matsushita
    AU  - Riki Kurokawa
    Y1  - 2013/12/10
    PY  - 2013
    N1  - https://doi.org/10.11648/j.cb.20130102.11
    DO  - 10.11648/j.cb.20130102.11
    T2  - Cell Biology
    JF  - Cell Biology
    JO  - Cell Biology
    SP  - 18
    EP  - 23
    PB  - Science Publishing Group
    SN  - 2330-0183
    UR  - https://doi.org/10.11648/j.cb.20130102.11
    AB  - 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 51 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.
    VL  - 1
    IS  - 2
    ER  - 

    Copy | Download

Author Information
  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama 350-0495, Japan

  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane, Hidaka-shi, Saitama 350-1241, Japan

  • Sections