Comprehensive analysis of TRIM type ubiquitin ligases in cell proliferation and differentiation

• Project/Area Number: 24390065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Hokkaido University
• Principal Investigator: HATAKEYAMA Shigetsugu 北海道大学, 医学(系)研究科(研究院), 教授 (70294973)
• Co-Investigator(Renkei-kenkyūsha): TSUKIYAMA Tadasuke 北海道大学, 大学院医学研究科, 助教 (20399819) ; TAKAHASHI Hidehisa 北海道大学, 大学院医学研究科, 講師 (30423544)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2013: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 細胞内シグナル伝達 / ユビキチン / 細胞増殖 / 細胞分化 / 転写 / がん

Outline of Final Research Achievements

TRIM family ubiquitin ligases are important for regulation of carcinogenesis in several cancers. It has been reported that TRIM family ubiquitin ligases regulate the activity of transcription factors in the process of cell proliferation and differentiation. By using proteomics analysis, we comprehensively analyzed TRIM family ubiquitin ligases which are related to ubiquitination of transcription factors. The analysis clarified the molecular mechanism in carcinogenesis of several cancers, maybe leading to the contribution to clinical applications for diagnosis and therapies.

Research Products

• [Journal Article] Molecular role of RNF43 in canonical and noncanonical Wnt signaling (2015)
  • Author(s): Tsukiyama, T., Fukui, A., Terai, S., Fujioka, Y., Shinada, K., Takahashi, H., Yamaguchi, T.P., Ohba, Y., Hatakeyama, S.
  • Journal Title: Mol. Cell. Biol. Volume: 未定
  • NAID: 120005672365
  • 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
• [Journal Article] MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex (2015)
  • Author(s): Takahashi, H., Takigawa, I., Watanabe, M., Anwar, D., Shibata, M., Tomomori-Sato, C., Sato, S., Ranjan, A., Seidel, C.W., Tsukiyama, T., Mizushima, W., Hayashi, M., Ohkawa, Y., Conaway, J.W., Conaway, R.C. and Hatakeyama, S
  • Journal Title: Nature Commun. Volume: 5 Issue: 1 Pages: 5941-5941
  • DOI: 10.1038/ncomms6941
  • NAID: 120005621881
  • 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] Oxidative stress regulates IL-4 gene expression in mast cells through the reduction of histone deacetylase (2015)
  • Author(s): Nakamaru, Y., Takagi, D., Homma, A., Hatakeyama, S., Fukuda, S.
  • Journal Title: Otolaryngol. Head Neck Surg. Volume: 152 Issue: 1 Pages: 48-52
  • DOI: 10.1177/0194599814559189
  • Peer Reviewed / Open Access
• [Journal Article] Siglec-15 is a potential therapeutic target for postmenopausal osteoporosis (2015)
  • Author(s): Kameda, Y., Takahata, M., Mikuni, S., Shimizu, T., Hamano, H., Angata, T., Hatakeyama, S., Kinjo, M. and Iwasaki, N.
  • Journal Title: Bone Volume: 71 Pages: 217-226
  • DOI: 10.1016/j.bone.2014.10.027
  • Peer Reviewed
• [Journal Article] Pathology of frontotemporal dementia with limb girdle muscular dystrophy caused by DNAJB6 mutation (2014)
  • Author(s): Yabe, I., Tanino, M., Yaguchi, H., Takiyama, A., Cai, H., Kanno, H., Takahashi, I., Hayashi, Y., Watanabe, M., Takahashi, H., Hatakeyama, S., Tanaka, S. and Sasaki, H.
  • Journal Title: Clin. Neurol. Neurosur. Volume: 127 Pages: 10-12
  • DOI: 10.1016/j.clineuro.2014.09.013
  • NAID: 120005540291
  • Peer Reviewed / Open Access
• [Journal Article] TRIM29 suppresses TWIST1 and invasive breast cancer behavior (2014)
  • Author(s): Ai, L., Wan-Ju Kim, W., Alpay, M., Tang, M., Pardo, C.E., Hatakeyama, S., May, W.S. , Kladde, M.P., Heldermon, C.D., Siegel, E.M. and Brown, K.D.
  • Journal Title: Cancer Res Volume: 74 Issue: 17 Pages: 4875-4887
  • DOI: 10.1158/0008-5472.can-13-3579
  • Peer Reviewed
• [Journal Article] TRIM29 as a novel prostate basal cell marker for diagnosis of prostate cancer (2014)
  • Author(s): Kanno, Y., Watanabe, M., Kimura, T., Nonomura, K., Tanaka, S. and Hatakeyama, S
  • Journal Title: Acta Histochem Volume: 116 Issue: 5 Pages: 708-712
  • DOI: 10.1016/j.acthis.2013.12.009
  • NAID: 120005472205
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 14-3-3 proteins sequester a pool of soluble TRIM32 ubiquitin ligase to repress autoubiquitination and cytoplasmic body formation (2013)
  • Author(s): Ichimura T, Taoka M, Shoji I, Kato H, Sato T, Hatakeyama S, Isobe T and Hachiya N
  • Journal Title: J. Cell. Sci. Volume: 126 Pages: 2014-2026
  • DOI: 10.1242/jcs.122069
  • Peer Reviewed
• [Journal Article] Siglec-15 Regulates Osteoclast Cytoskeletal Organization in Association with Signaling Adaptor DAP12 (2013)
  • Author(s): Kameda Y, Takahata M, Komatsu M, Mikuni S, Hatakeyama S, Shimizu T, Angata T, Kinjo M, Minami A and Iwasaki N
  • Journal Title: J. Bone Mineral Res. Volume: 28 Issue: 12 Pages: 2463-2475
  • DOI: 10.1002/jbmr.1989
  • Peer Reviewed
• [Journal Article] Identification of anti-Sez6l2 antibody in a patient with cerebellar ataxia and retinopathy (2013)
  • Author(s): Yaguchi H, Yabe I, Takahashi H, Okumura F, Takeuchi A, Horiuchi, K, Kan T, Kanda, A, Saito W, Matsumoto M, Nakayama KI, Hatakeyama S and Sasaki H
  • Journal Title: J. Neurol. Volume: 261 Issue: 1 Pages: 224-226
  • DOI: 10.1007/s00415-013-7134-5
  • Peer Reviewed
• [Journal Article] 14-3-3 proteins sequester a pool of soluble TRIM32 ubiquitin ligase to repress autoubiquitination (2013)
  • Author(s): Ichimura, T., et al.
  • Journal Title: J. Cell Sci. Volume: (in press)
  • Peer Reviewed
• [Journal Article] Activation of double-stranded RNA-activated protein kinase (PKR) by interferon-stimulated gene 15 (ISG15) modification down-regulates protein translation (2013)
  • Author(s): Okumura, F., Okumura, AJ., Uematsu, K., Hatakeyama, S., Zhang, DE., Kamura, T
  • Journal Title: J Biol Chem Volume: 288(4) Issue: 4 Pages: 2839-47
  • DOI: 10.1074/jbc.m112.401851
  • Peer Reviewed
• [Journal Article] Ubiquitin-mediated regulation of JAK-STAT signaling in embryonic stem cells. (2012)
  • Author(s): Hatakeyama s.
  • Journal Title: JAK-STAT Volume: 1 Pages: 168-175
  • Peer Reviewed
• [Journal Article] TRIM45 negatively regulates NF-kB-mediated transcription and suppresses cell prolifration. (2012)
  • Author(s): Shibata, M., Sato, T., Nukiwa, R., Ariga, T. and Hatakeyama, S.
  • Journal Title: Biophys. Res. Commun. Volume: 423 Issue: 1 Pages: 104-109
  • DOI: 10.1016/j.bbrc.2012.05.090
  • Peer Reviewed
• [Journal Article] TRIM59 interacts with ECSIT and negatively regulates NF-kB and IRF-3/7-mediated signal pathway. (2012)
  • Author(s): Kondo, T., Watanabe, M. and Hatakeyama, S
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 422 Issue: 3 Pages: 501-507
  • DOI: 10.1016/j.bbrc.2012.05.028
  • Peer Reviewed
• [Journal Article] Ymer acts as a multufunctional regulator in NF-kB and Fas signaling pathways (2012)
  • Author(s): Tsukiyama, T., et al
  • Journal Title: Mol.Med. Volume: (in press) Issue: 4 Pages: 587-597
  • DOI: 10.2119/molmed.2011.00435
  • Peer Reviewed
• [Journal Article] TRIM6 interacts with c-Myc and maintains pluripotency of mouse embryonal stem cells (2012)
  • Author(s): Sato T, Okumura F, Ariga T, Hatakeyama S
  • Journal Title: J Cell Sci Volume: (in press) Pages: 1544-1555
  • DOI: 10.1242/jcs.095273
  • Peer Reviewed
• [Presentation] メディエーター複合体による転写伸長制御 (2014)
  • Author(s): 高橋秀尚, 瀧川一学, 渡部昌, Delnur Anwar, 柴田美音, 佐藤チエリ, 佐藤滋生, Amol Ranjan, Chris W Seidel, 築山忠維, 林正康、大川恭行, Joan W Conaway, Ronald C Conaway, 畠山鎮次
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-11-25 – 2014-11-28
• [Presentation] Med26はLittle elongation complexをリクルートすることでsmall nuclear RNA遺伝子の発現を制御する (2014)
  • Author(s): 高橋秀尚, 瀧川一学, 渡部昌, Anwar Delnur, 柴田美音, 佐藤チエリ, 佐藤滋生, Ranjan Amol, Seidel Chris, 築山忠維, 林正康, 大川恭行, Conaway Joan, Conaway Ronald, 畠山鎮次
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] TRIMタンパク質による脂肪細胞分化制御 (2014)
  • Author(s): 渡部昌, 髙橋秀尚, 畠山鎮次
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] TRIM29はヒストンH2AXのリン酸化を介してDNA二本鎖切断修復を制御する (2014)
  • Author(s): 桝田安志, 髙橋秀尚, Conaway Ronald C., Conaway Joan W., 畠山鎮次
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 京都国際会議場（京都府・京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Tripartite motif protein39(TRIM39)の機能解析 (2014)
  • Author(s): 鈴木正宣，渡部昌，中丸裕爾，福田諭，畠山鎮次
  • Organizer: 第79回日本インターフェロン・サイトカイン学会学術集会
  • Place of Presentation: 北海道大学（北海道・札幌市）
  • Year and Date: 2014-06-19 – 2014-06-20
• [Presentation] Regulation of cellular functions by TRIM proteins (2013)
  • Author(s): Hatakeyama, S.
  • Organizer: The 35th Naito Conference: The Ubiquitin-Protesome System: from Basic Mechanisms to Pathophysiological Roles
  • Place of Presentation: シャトレーゼ ガトー キングダム サッポロ（札幌）
  • Invited
• [Presentation] Involvement of linear polyubiquitylation in PPARγ transcriptional activity (2013)
  • Author(s): Watanabe, M., Takayashi, H., Hatakeyama, S.
  • Organizer: The 35th Naito Conference: The Ubiquitin-Protesome System: from Basic Mechanisms to Pathophysiological Roles
  • Place of Presentation: シャトレーゼ ガトー キングダム サッポロ（札幌）
• [Presentation] Functional analysis of a novel multiprotein complex containing ataxia telangiectasia group D-complementing (ATDC) gene product, TRIM29 (2013)
  • Author(s): Masuda, Y., Takahashi, H., Matsumoto, M., Nakayama, K., Hatakeyama, S.
  • Organizer: The 35th Naito Conference: The Ubiquitin-Protesome System: from Basic Mechanisms to Pathophysiological Roles
  • Place of Presentation: シャトレーゼ ガトー キングダム サッポロ（札幌）
• [Presentation] TRIMタンパク質の多彩な機能 (2013)
  • Author(s): 畠山鎮次
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Invited
• [Presentation] ATDCはヒストンH2A.Xのリン酸化とヒストンH4のアセチル化を介してDNA日本鎖切断修復を制御する (2013)
  • Author(s): 桝田安志、畠山鎮次
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] がん抑制遺伝子RNF43は異なるメカニズムによってWnt/beta-catenin経路とnoncanonical Wnt経路を抑制する (2013)
  • Author(s): 築山忠維、畠山鎮次
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（横浜）
• [Presentation] RNF43遺伝子変異によるがん抑制遺伝子からがん遺伝子への機能転換 (2013)
  • Author(s): 築山 忠維，福井 彰雅，寺井 小百合，藤岡 容一朗，品田 恵佐，Yamaguchi Terry，大場 雄介，畠山 鎮次
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド（神戸）
• [Presentation] ランチタイム教育講演2 「免疫と癌を制御するTRIM型ユビキチンリガーゼ」 (2012)
  • Author(s): 畠山 鎮次
  • Organizer: 第40回日本臨床免疫学会総会
  • Place of Presentation: 京王プラザホテル(北海道)(招待講演)
  • Year and Date: 2012-09-28
• [Presentation] シンポジウム : オートファジー・プロテオステイシスとがん「TRIM proteins and cancer」 (2012)
  • Author(s): Hatakeyama, S
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-19
• [Presentation] RNF43はNEDLlと結合し, p53依存性の転写を調節する(ポスター) (2012)
  • Author(s): 築山忠雄,畠山鎮次
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: ロイトン札幌(北海道)
  • Year and Date: 2012-09-19
• [Presentation] Med26はLittle elongation complexをリクルートすることでsmall nuclear RNA遺伝子の発現を制御する (2012)
  • Author(s): 高橋秀尚, 佐藤智信, Conaway, J. W., Conaway, R. C., 畠山鎮次
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] double-stranded RNA-activated protein kinase (PKR)はinterferon stimulated gene 15(ISG15)修飾により活性化され、キャップ構造依存性のタンパク質翻訳を抑制する (2012)
  • Author(s): 奥村文彦, 畠山鎮次, ドンガーザン, 嘉村巧
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] RNF43はcanonical/noncanonical Wntシグナルの両方を抑制する(ポスター) (2012)
  • Author(s): Tadasuke Tsukiyama, Akimasa Fukui, Sayuri Terai, Keisuke Shinada, Shigetsugu Hatakeyama
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] Human Mediator subunit Med26 plays a role in recruitment of "Little elongation complex" to small nuclear RNA genes (ポスター) (2012)
  • Author(s): Hidehisa Takahashi, Joan w. Conaway, Ronald c. Conaway, Shigetsugu Hatakeyama
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] Med26はLittle elongation complexをリクルートすることでsmall nuclear RNA遺伝子の発現を制御する (2012)
  • Author(s): 高橋秀尚、Joan w. Conaway、Ronald c. Conaway、畠山 鎮次
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] TRIM29によるTRRAP/Tip60複合体の機能制御とがん化との関わり (2012)
  • Author(s): 桝田安志、高橋秀尚、畠山鎮次
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Presentation] TRIMタンパク質の多様性と機能 (2012)
  • Author(s): 畠山 鎮次
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡 (福岡)
• [Book] がん基盤生物学 ー革新的シーズ育成に向けてー (2013)
  • Author(s): 清木元治
  • Total Pages: 336
  • Publisher: 南山堂
• [Book] 標準生化学 (2012)
  • Author(s): 藤田道也
  • Total Pages: 2012
  • Publisher: 医学書院
• [Patent(Industrial Property Rights)] 前立腺基底細胞の検出方法 (2012)
  • Inventor(s): 畠山鎮次, 田中伸哉
  • Industrial Property Rights Holder: 畠山鎮次, 田中伸哉
  • Filing Date: 2012-12-30