Regulation of signal transduction by TRIM family proteins

• Project/Area Number: 15H04690
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Hokkaido University
• Principal Investigator: Hatakeyama Shigetsugu 北海道大学, 医学研究院, 教授 (70294973)
• Co-Investigator(Renkei-kenkyūsha): TAKAHASHI Hidehisa 横浜市立大学, 大学院医学研究科, 教授 (20399819) ; WATANABE Masashi 北海道大学, 医学研究院, 助教 (10632424)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: ユビキチン / シグナル伝達 / タンパク質分解 / タンパク質修飾 / 転写

Outline of Final Research Achievements

Our previous studies have shown the importance of TRIM family ubiquitin ligase in intracellular signal transduction. Especially, we showed that TRIM family ubiquitin ligase regulates signal transduction involved in cell proliferation and differentiation. Therefore, in this application, we identified and analyzed TRIM family ubiquitin ligases which regulates the ubiquitination in various intracellular signalling pathways. Furthermore, we identified and analyzed candidate genes regulating metabolism and immune signal by comprehensive knockdown of TRIM family genes using their siRNA library.

Research Products

• [Int'l Joint Research] Shanghai Jiao Tong University/Tsinghua University(中国)
• [Int'l Joint Research] Northwestern University(米国)
• [Journal Article] TRIM59 promotes gliomagenesis by inhibiting TC45 dephosphorylation of STAT3 (2018)
  • Author(s): Sang, Y., Li, Y., Song, L., Alvarez, A.A., Zhang, W., Lv, D., Tang, J., Liu, F., Chang, Z., Hatakeyama, S., Hu, B., Cheng, S. and Feng, H.
  • Journal Title: Cancer Res. Volume: 78 Issue: 7 Pages: 1792-1804
  • DOI: 10.1158/0008-5472.can-17-2774
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] TRIM Family Proteins: Roles in Autophagy, Immunity and Carcinogenesis. (2017)
  • Author(s): Hatakeyama, S
  • Journal Title: Trends Biochem. Sci. Volume: 42 Issue: 4 Pages: 297-311
  • DOI: 10.1016/j.tibs.2017.01.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fine-tuning of thymocyte development by ubiquitination-mediated stability control of the ESCRT protein CHMP5 (2017)
  • Author(s): Watanabe, M. and Hatakeyama, S.
  • Journal Title: Cell. Moll. Immnol. Volume: 14 Issue: 12 Pages: 957-959
  • DOI: 10.1038/cmi.2017.91
  • Peer Reviewed
• [Journal Article] TRIM proteins and diseases. (2017)
  • Author(s): Watanabe, M. and Hatakeyama, S
  • Journal Title: J. Biochem. Volume: 161 Pages: 135-144
  • DOI: 10.1093/jb/mvw087
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of intestinal homeostasis by theulcerative colitis-associated gene RNF186. (2017)
  • Author(s): Fujimoto K, Kinoshita M, Tanaka H, Okuzaki D, Shimada Y, Kayama H, Okumura R, Furuta Y, Narazaki M, Tamura A, Hatakeyama S, Ikawa M, Tsuchiya K, Watanabe M, Kumanogoh A, Tsukita S, Takeda K
  • Journal Title: Mucosal Immunol. Volume: 10 Issue: 2 Pages: 446-459
  • DOI: 10.1038/mi.2016.58
  • Peer Reviewed
• [Journal Article] A leukemogenic kinase, FIP1L1-PDGFRA, and a SUMO E3 ligase, PIAS1, form a positive crosstalk via their enzymatic activities. (2017)
  • Author(s): M. Ibata, J. Iwasaki, Y. Fujioka, K. Nakagawa, S. Darmanin, M. Onozawa, D. Hashimoto, Y. Ohba, S. Hatakeyama, T. Teshima and T. Kondo.
  • Journal Title: Cancer Sci. Volume: 108 Issue: 2 Pages: 200-207
  • DOI: 10.1111/cas.13129
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Early evidence for the role of TRIM29 in multiple cancer models (2016)
  • Author(s): Hatakeyama, S.
  • Journal Title: Expert Opinion on Therapeutic Targets Volume: 20 Pages: 767-770
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Role of apolipoprotein B100 and oxidized low-density lipoprotein in the monocyte tissue factor induction mediated by anti-b2 glycoprotein I antibodies. (2016)
  • Author(s): Otomo K, Amengual O, Fujieda Y, Nakagawa H, Kato M, Oku K, Horita T, Yasuda S, Matsumoto M, Nakayama KI, Hatakeyama S, Koike T, Atsumi T
  • Journal Title: Lupus Volume: Epub ahead Issue: 12 Pages: 1288-1298
  • DOI: 10.1177/0961203316638165
  • Peer Reviewed / Open Access
• [Journal Article] Ribophorin II is involved in the tissue factor expression mediated by phosphatidylserine-dependent antiprothrombin antibody on monocytes (2016)
  • Author(s): Fujieda Y., Amengual O., Matsumoto M., Kuroki K., Takahashi H., Kono M., Kurita Y., Otomo K., Kato M., Oku K., Bohgaki T., Horita T., Yasuda S., Maenaka K., Hatakeyama S., Nakayama K.I. and Atsumi T. et al.
  • Journal Title: Rheumatology Volume: 印刷中 Issue: 6 Pages: 1117-1126
  • DOI: 10.1093/rheumatology/kew005
  • Peer Reviewed / Open Access
• [Journal Article] p53 represses the transcription of snRNA genes by preventing the formation of little elongation complex (2016)
  • Author(s): Anwar, D., Takahashia, H., Watanabe, M., Suzuki, M., Fukuda, S., Hatakeyama, S.
  • Journal Title: Biochim. Biophys. Acta-Gene Regul. Mech. Volume: 1859 Issue: 8 Pages: 975-982
  • DOI: 10.1016/j.bbagrm.2016.06.001
  • NAID: 120006328999
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The novel heart-specific RING finger protein 207 is involved in energy metabolism in cardiomyocytes. (2016)
  • Author(s): Mizushima, W., Takahashi , H., Watanabe, M., Kinugawa, S., Matsushima, S., Takada, S., Yokota, T., Furihata, T., Matsumoto, J., Tsuda, M., Chiba, I., Nagashima, S., Yanagi, S., Matsumoto, M., Nakayama, K.I., Tsutsui, H. and Hatakeyama, S.
  • Journal Title: J. Mol. Cell. Cardiol. Volume: 100 Pages: 43-53
  • DOI: 10.1016/j.yjmcc.2016.09.013
  • NAID: 120006360069
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] TRIM39 negatively regulates the NFκB-mediated signaling pathway through stabilization of Cactin (2016)
  • Author(s): Suzuki M, Watanabe M, Nakamaru Y, Takagi D, Takahashi H, Fukuda S, Hatakeyama S.
  • Journal Title: Cell Mol Life Sci. Volume: ７３ Issue: 5 Pages: 1085-1101
  • DOI: 10.1007/s00018-015-2040-x
  • NAID: 120005981342
  • Peer Reviewed / Open Access
• [Journal Article] The TRIM-FLMN protein TRIM45 directly interacts with RACK1 and negatively regulates PKC-mediated signaling pathway (2015)
  • Author(s): Sato, T., Takahashi, H., Hatakeyama, S., Iguchi, A. and Ariga, T
  • Journal Title: Oncogene Volume: 34 Issue: 10 Pages: 1280-1291
  • DOI: 10.1038/onc.2014.68
  • Peer Reviewed
• [Journal Article] Molecular role of RNF43 in canonical and noncanonical Wnt signaling (2015)
  • Author(s): T. Tsukiyama,et al.
  • Journal Title: Mol. Cell. Biol. Volume: in press Issue: 11 Pages: 2007-2023
  • DOI: 10.1128/mcb.00159-15
  • Peer Reviewed / Open Access
• [Journal Article] The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipocyte activator PPAR gamma. (2015)
  • Author(s): Watanabe, M., Takahashi, H., Saeki, Y., Ozaki, T., Itoh, S., Suzuki, M., Mizushima, W., Tanaka, K. and Hatakeyama, S.
  • Journal Title: eLIFE Volume: 4
  • DOI: 10.7554/elife.05615
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin. (2015)
  • Author(s): Masuda, Y., Takahashi, H., Sato, S., Tomonori-Sato, C., Saraf, A., Washburn, M.P., Florens, L., Conaway, R.C., Conaway, J.W. and Hatakeyama, S.
  • Journal Title: Nature Commun. Volume: 6 Issue: 1 Pages: 7299-7299
  • DOI: 10.1038/ncomms8299
  • NAID: 120005647269
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] TRIM29 regulates the p63-mediated pathway in cervical cancer cells. (2015)
  • Author(s): Masuda, Y., Takahashi, H. and Hatakeyama, S.
  • Journal Title: Biochim. Biophy. Acta-Mol. Cell Res Volume: 1853 Issue: 10 Pages: 2296-2305
  • DOI: 10.1016/j.bbamcr.2015.05.035
  • NAID: 120005906885
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The inflammatory cytokine IL-1b is involved in bladder remodeling after bladder outlet obstruction in mice (2015)
  • Author(s): Kanno, Y., Mitsui, T., Kitta, T., Moriya, K., Tsukiyama, T., Hatakeyama, S. and Nonomura, K.
  • Journal Title: Neurouro. Urodyn. Volume: 未定 Issue: 3 Pages: 277-381
  • DOI: 10.1002/nau.22721
  • Peer Reviewed
• [Presentation] TRIMタンパク質の機能と病理学的解析 (2018)
  • Author(s): 畠山鎮次
  • Organizer: 第１回ユビキチン研究会
• [Presentation] ＴＲＩＭファミリータンパク質が関与する疾患 (2017)
  • Author(s): 畠山鎮次
  • Organizer: 第24回分子皮膚科学フォーラム
  • Invited
• [Presentation] ＴＲＩＭファミリータンパク質による細胞機能制御 (2017)
  • Author(s): 畠山鎮次
  • Organizer: GU Cancer Forum 2017
  • Invited
• [Presentation] Functions of TRIM family proteins in metabolism and carcinogenesis (2016)
  • Author(s): Shigetsugu Hatakeyama
  • Organizer: International Symposium for New Aspects of the Ubiquitin Research
  • Place of Presentation: 京都大学基礎医学記念講堂（京都府京都市）
  • Int'l Joint Research / Invited
• [Presentation] TRIMファミリーユビキチンリガーゼによる生体制御機構 (2015)
  • Author(s): 畠山鎮次
  • Organizer: 日本生化学会
  • Place of Presentation: 神戸ポートピアホテル（兵庫県・神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Book] Ubiquitin-conjugating enzymes (E2s): Adnances in Medicine and Biology Vol 120 (2017)
  • Author(s): Watanabe, M. and Hatakeyama, S.
  • Total Pages: 23
  • Publisher: Nova Science Publishers