Feb. 2021, 北海道大学大学院医学研究院, 優秀論文賞　　　　　　　　　　　　　　　
築山忠維

Dec. 2015, 公益財団法人 日本膵臓病研究財団, 膵臓病研究奨励賞　　　　　　　　　　　　　　　
築山 忠維

New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis
Tadasuke Tsukiyama
In Vitro Cellular & Developmental Biology - Animal, Springer Science and Business Media LLC, 21 Feb. 2024, [Peer-reviewed], [Invited], [Lead author, Corresponding author]
English, Scientific journal, Abstract

Wnt signaling plays a crucial role in embryonic development and homeostasis maintenance. Delicate and sensitive fine-tuning of Wnt signaling based on the proper timings and positions is required to balance cell proliferation and differentiation and maintain individual health. Therefore, homeostasis is broken by tissue hypoplasia or tumor formation once Wnt signal dysregulation disturbs the balance of cell proliferation. The well-known regulatory mechanism of Wnt signaling is the molecular reaction associated with the cytoplasmic accumulation of effector β-catenin. In addition to β-catenin, most Wnt effector proteins are also regulated by ubiquitin-dependent modification, both qualitatively and quantitatively. This review will explain the regulation of the whole Wnt signal in four regulatory phases, as well as the different ubiquitin ligases and the function of deubiquitinating enzymes in each phase. Along with the recent results, the mechanism by which RNF43 negatively regulates the surface expression of Wnt receptors, which has recently been well understood, will be detailed. Many RNF43 mutations have been identified in pancreatic and gastrointestinal cancers and examined for their functional alteration in Wnt signaling. Several mutations facilitate or activate the Wnt signal, reversing the RNF43 tumor suppressor function into an oncogene. RNF43 may simultaneously play different roles in classical multistep tumorigenesis, as both wild-type and mutant RNF43 suppress the p53 pathway. We hope that the knowledge obtained from further research in RNF43 will be applied to cancer treatment in the future despite the fully unclear function of RNF43., 42063426

Wnt/β-catenin signaling stabilizes hemidesmosomes in keratinocytes
Kosumi, Hideyuki, Watanabe, Mika, Shinkuma, Satoru, Fujimura, Yu, Tsukiyama, Tadasuke, Donati, Giacomo, Iwata, Hiroaki, Ujiie, Hideyuki, Natsuga, Ken M
Journal of Investigative Dermatology, 142, 6, 1576, 1586, 01 Jun. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Hemidesmosomes (HDs) are adhesion complexes that promote epithelial-stromal attachment in stratified and complex epithelia, including the epidermis. In various biological processes, such as differentiation and migration of epidermal keratinocytes during wound healing or carcinoma invasion, quick assembly and disassembly of HDs are prerequisites. In this study, we show that inhibition of Wnt/β-catenin signaling disturbs HD organization in keratinocytes. Screening with inhibitors identified the depletion of HD components and HD-like structures through Wnt inhibition, but keratinocyte differentiation was not affected. Wnt inhibition significantly diminished plectin and type XVII collagen expression in the basal side of Wnt-inhibited cells and the dermo-epidermal junction of the Wnt-inactive murine basal epidermis. Similar to Wnt inhibition, PLEC-knockout cells or cells with plectin-type XVII collagen binding defects showed type XVII collagen reduction in the basal side of the cells, implying the possible involvement of Wnt/β-catenin signaling in HD assembly. Atypical protein kinase C inhibition ameliorated the phenotypes of Wnt-inhibited cells. These findings show that Wnt/β-catenin signaling regulates the localization of HD components in keratinocytes and that the atypical protein kinase C pathway is involved in Wnt inhibition‒induced HD disarrangement. Our study suggests that the Wnt signaling pathway could be a potential therapeutic target for treating HD-defective diseases, such as epidermolysis bullosa.

Post‐translational Wnt receptor regulation: Is the fog slowly clearing?
Tadasuke Tsukiyama, Bon‐Kyoung Koo, Shigetsugu Hatakeyama
BioEssays, 43, 4, 2000297, 2000297, Wiley, 11 Feb. 2021, [Peer-reviewed], [Invited], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal, Wnt signaling plays pivotal roles during our entire lives, from conception to death, through the regulation of morphogenesis in developing embryos and the maintenance of tissue homeostasis in adults. The regulation of Wnt signaling occurs on several levels: at the receptor level on the plasma membrane, at the β-catenin protein level in the cytoplasm, and through transcriptional regulation in the nucleus. Several recent studies have focused on the mechanisms of Wnt receptor regulation, following the discovery that the Wnt receptor frizzled (Fzd) is a target of the ubiquitin ligases, RNF43 and ZNRF3. RNF43 and ZNRF3 are homologous genes that are mutated in several cancers. The details underlying their mechanism of action continue to unfold, while at the same time raising many new questions. In this review, we discuss advances and controversies in our understanding of Wnt receptor regulation., 24556193

A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis
Tadasuke Tsukiyama, Juqi Zou, Jihoon Kim, Shohei Ogamino, Yuki Shino, Takamasa Masuda, Alessandra Merenda, Masaki Matsumoto, Yoichiro Fujioka, Tomonori Hirose, Sayuri Terai, Hidehisa Takahashi, Tohru Ishitani, Keiichi I. Nakayama, Yusuke Ohba, Bon-Kyoung Koo, Shigetsugu Hatakeyama
Nature Communications, 11, 1, 4586, 4586, Springer Science and Business Media LLC, 15 Sep. 2020, [Peer-reviewed], [Lead author, Corresponding author], [International Magazine]
English, Scientific journal,
Frequent mutation of the tumour suppressor RNF43 is observed in many cancers, particularly colon malignancies. RNF43, an E3 ubiquitin ligase, negatively regulates Wnt signalling by inducing degradation of the Wnt receptor Frizzled. In this study, we discover that RNF43 activity requires phosphorylation at a triplet of conserved serines. This phospho-regulation of RNF43 is required for zebrafish development and growth of mouse intestinal organoids. Cancer-associated mutations that abrogate RNF43 phosphorylation cooperate with active Ras to promote tumorigenesis by abolishing the inhibitory function of RNF43 in Wnt signalling while maintaining its inhibitory function in p53 signalling. Our data suggest that RNF43 mutations cooperate with KRAS mutations to promote multi-step tumorigenesis via the Wnt-Ras-p53 axis in human colon cancers. Lastly, phosphomimetic substitutions of the serine trio restored the tumour suppressive activity of extracellular oncogenic mutants. Therefore, harnessing phospho-regulation of RNF43 might be a potential therapeutic strategy for tumours with RNF43 mutations.

The role of Mediator and Little Elongation Complex in transcription termination.
Hidehisa Takahashi, Amol Ranjan, Shiyuan Chen, Hidefumi Suzuki, Mio Shibata, Tomonori Hirose, Hiroko Hirose, Kazunori Sasaki, Ryota Abe, Kai Chen, Yanfeng He, Ying Zhang, Ichigaku Takigawa, Tadasuke Tsukiyama, Masashi Watanabe, Satoshi Fujii, Midori Iida, Junichi Yamamoto, Yuki Yamaguchi, Yutaka Suzuki, Masaki Matsumoto, Keiichi I Nakayama, Michael P Washburn, Anita Saraf, Laurence Florens, Shigeo Sato, Chieri Tomomori-Sato, Ronald C Conaway, Joan W Conaway, Shigetsugu Hatakeyama
Nature communications, 11, 1, 1063, 1063, 26 Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Mediator is a coregulatory complex that regulates transcription of Pol II-dependent genes. Previously, we showed that human Mediator subunit MED26 plays a role in the recruitment of Super Elongation Complex (SEC) or Little Elongation Complex (LEC) to regulate the expression of certain genes. MED26 plays a role in recruiting SEC to protein-coding genes including c-myc and LEC to small nuclear RNA (snRNA) genes. However, how MED26 engages SEC or LEC to regulate distinct genes is unclear. Here, we provide evidence that MED26 recruits LEC to modulate transcription termination of non-polyadenylated transcripts including snRNAs and mRNAs encoding replication-dependent histone (RDH) at Cajal bodies. Our findings indicate that LEC recruited by MED26 promotes efficient transcription termination by Pol II through interaction with CBC-ARS2 and NELF/DSIF, and promotes 3' end processing by enhancing recruitment of Integrator or Heat Labile Factor to snRNA or RDH genes, respectively.

Type XVII collagen coordinates proliferation in the interfollicular epidermis
Mika Watanabe, Ken Natsuga, Wataru Nishie, Yasuaki Kobayashi, Giacomo Donati, Shotaro Suzuki, Yu Fujimura, Tadasuke Tsukiyama, Hideyuki Ujiie, Satoru Shinkuma, Hideki Nakamura, Masamoto Murakami, Michitaka Ozaki, Masaharu Nagayama, Fiona M. Watt, Hiroshi Shimizu
ELIFE, 6, e26635, 1, 24, Jul. 2017, [Peer-reviewed]
English, Scientific journal

The inflammatory cytokine IL-1 is involved in bladder remodeling after bladder outlet obstruction in mice
Yukiko Kanno, Takahiko Mitsui, Takeya Kitta, Kimihiko Moriya, Tadasuke Tsukiyama, Shigetsugu Hatakeyama, Katsuya Nonomura
NEUROUROLOGY AND URODYNAMICS, 35, 3, 377, 381, Mar. 2016, [Peer-reviewed]
English, Scientific journal

Molecular Role of RNF43 in Canonical and Noncanonical Wnt Signaling
Tadasuke Tsukiyama, Akimasa Fukui, Sayuri Terai, Yoichiro Fujioka, Keisuke Shinada, Hidehisa Takahashi, Terry P. Yamaguchi, Yusuke Ohba, Shigetsugu Hatakeyama
MOLECULAR AND CELLULAR BIOLOGY, 35, 11, 2007, 2023, Jun. 2015, [Peer-reviewed]
English, Scientific journal

MED26 regulates the transcription of snRNA genes through the recruitment of little elongation complex
Hidehisa Takahashi, Ichigaku Takigawa, Masashi Watanabe, Delnur Anwar, Mio Shibata, Chieri Tomomori-Sato, Shigeo Sato, Amol Ranjan, Chris W. Seidel, Tadasuke Tsukiyama, Wataru Mizushima, Masayasu Hayashi, Yasuyuki Ohkawa, Joan W. Conaway, Ronald C. Conaway, Shigetsugu Hatakeyama
NATURE COMMUNICATIONS, 6, 5941, Jan. 2015, [Peer-reviewed]
English, Scientific journal

Variation in the bacterial conditions inside cages is correlated with intracage humidity and ammonia levels.　　　　　　　　　　　　　　　
Tosa N, Yoshimatsu K, Tadasuke Tsukiyama, Hatakeyama S, Arikawa J
Lab Animal and Environ, 21, 2, 87, 98, 2013, [Peer-reviewed]
English, Scientific journal

Ymer Acts as a Multifunctional Regulator in Nuclear Factor-kappa B and Fas Signaling Pathways
Tadasuke Tsukiyama, Mayuko Matsuda-Tsukiyama, Miyuki Bohgaki, Sayuri Terai, Shinya Tanaka, Shigetsugu Hatakeyama
MOLECULAR MEDICINE, 18, 4, 587, 597, Apr. 2012, [Peer-reviewed]
English, Scientific journal

Mice lacking Wnt2b are viable and display a postnatal olfactory bulb phenotype
Tadasuke Tsukiyama, Terry P. Yamaguchi
NEUROSCIENCE LETTERS, 512, 1, 48, 52, Mar. 2012, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

TRIM29 negatively regulates p53 via inhibition of Tip60
Takuya Sho, Tadasuke Tsukiyama, Tomonobu Sato, Takeshi Kondo, Jun Cheng, Takashi Saku, Masahiro Asaka, Shigetsugu Hatakeyama
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1813, 6, 1245, 1253, Jun. 2011, [Peer-reviewed]
English, Scientific journal

The canonical Wnt signaling pathway is not involved in renal cyst development in the kidneys of inv mutant mice
Noriyuki Sugiyama, Tadasuke Tsukiyama, Terry P. Yamaguchi, Takahiko Yokoyama
KIDNEY INTERNATIONAL, 79, 9, 957, 965, May 2011, [Peer-reviewed]
English, Scientific journal

RNF43 interacts with NEDL1 and regulates p53-mediated transcription
Keisuke Shinada, Tadasuke Tsukiyama, Takuya Sho, Fumihiko Okumura, Masahiro Asaka, Shigetsugu Hatakeyama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 404, 1, 143, 147, Jan. 2011, [Peer-reviewed]
English, Scientific journal

TRIM24 mediates ligand-dependent activation of androgen receptor and is repressed by a bromodomain-containing protein, BRD7, in prostate cancer cells
Misato Kikuchi, Fumihiko Okumura, Tadasuke Tsukiyama, Masashi Watanabe, Naoto Miyajima, Junji Tanaka, Masahiro Imamura, Shigetsugu Hatakeyama
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1793, 12, 1828, 1836, Dec. 2009, [Peer-reviewed]
English, Scientific journal

TRIM31 interacts with p52(Shc) and inhibits Src-induced anchorage-independent growth
Masashi Watanabe, Tadasuke Tsukiyama, Shigetsugu Hatakeyama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 388, 2, 422, 427, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Ubiquitin-Conjugating Enzyme UBE2Q2 Suppresses Cell Proliferation and Is Down-Regulated in Recurrent Head and Neck Cancer
Hiroyuki Maeda, Naoto Miyajima, Satoshi Kano, Tadasuke Tsukiyama, Fumihiko Okumura, Satoshi Fukuda, Shigetsugu Hatakeyama
MOLECULAR CANCER RESEARCH, 7, 9, 1553, 1562, Sep. 2009, [Peer-reviewed]
English, Scientific journal

Wnt2/2b and beta-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the Foregut
Ashley M. Goss, Ying Tian, Tadasuke Tsukiyama, Ethan David Cohen, Diane Zhou, Min Min Lu, Terry P. Yamaguchi, Edward E. Morrisey
DEVELOPMENTAL CELL, 17, 2, 290, 298, Aug. 2009, [Peer-reviewed]
English, Scientific journal

Embryonic hair follicle fate change by augmented beta-catenin through Shh and Bmp signaling
Kentaro Suzuki, Yuji Yamaguchi, Mylah Villacorte, Kenichiro Mihara, Masashi Akiyama, Hiroshi Shimizu, Makoto M. Taketo, Naomi Nakagata, Tadasuke Tsukiyama, Terry P. Yamaguchi, Walter Birchmeier, Shigeaki Kato, Gen Yamada
DEVELOPMENT, 136, 3, 367, 372, Feb. 2009, [Peer-reviewed]
English, Scientific journal

Inhibition of NF-kappa B signaling via tyrosine phosphorylation of Ymer
Hiroyuki Kameda, Masashi Watanabe, Miyuki Bohgaki, Tadasuke Tsukiyama, Shigetsugu Hatakeyama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 378, 4, 744, 749, Jan. 2009, [Peer-reviewed]
English, Scientific journal

Involvement of Ymer in suppression of NF-kappaB activation by regulated interaction with lysine-63-linked polyubiquitin chain.
Bohgaki M, Tsukiyama T, Nakajima A, Maruyama S, Watanabe M, Koike T, Hatakeyama S
Biochimica et biophysica acta, 1783, 826, 837, 5, May 2008, [Peer-reviewed]

Involvement of Ymer in suppression of NF-kappa B activation by regulated interaction with lysine-63-linked polyubiquitin chain
Miyuki Bohgaki, Tadasuke Tsukiyama, Ayako Nakajima, Satoru Maruyama, Masashi Watanabe, Takao Koike, Shigetsugu Hatakeyama
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1783, 5, 826, 837, May 2008, [Peer-reviewed]
English, Scientific journal

Ro52 functionally interacts with IgG1 and regulates its quality control via the ERAD system
Mutsumi Takahata, Miyuki Bohgaki, Tadasuke Tsukiyama, Takeshi Kondo, Masahiro Asaka, Shigetsugu Hatakeyama
MOLECULAR IMMUNOLOGY, 45, 7, 2045, 2054, Apr. 2008, [Peer-reviewed]
English, Scientific journal

Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA
Satoru Maruyama, Naoto Miyajima, Miyuki Bohgaki, Tadasuke Tsukiyama, Masahiko Shigemura, Katsuya Nonomura, Shigetsugu Hatakeyama
MOLECULAR AND CELLULAR BIOCHEMISTRY, 307, 1-2, 73, 82, Jan. 2008, [Peer-reviewed]
English, Scientific journal

Ligand-dependent transcription of estrogen receptor alpha is mediated by the ubiquitin ligase EFP
Ayako Nakajima, Satoru Maruyama, Miyuki Bohgaki, Naoto Miyajima, Tadasuke Tsukiyama, Noriaki Sakuragi, Shigetsugu Hatakeyama
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 357, 1, 245, 251, May 2007, [Peer-reviewed]
English, Scientific journal

Establishment of a newly improved detection system for NF-kappa B activity
Mayuko Matsuda, Tadasuke Tsukiyama, Miyuki Bohgaki, Katsuya Nonomura, Shigetsugu Hatakeyama
IMMUNOLOGY LETTERS, 109, 2, 175, 181, Apr. 2007, [Peer-reviewed]
English, Scientific journal

Protection of vincristine-induced neuropathy by Wld(S) expression and the independence of the activity of Nmnat1
Masashi Watanabe, Tadasuke Tsukiyama, Shigetsugu Hatakeyama
NEUROSCIENCE LETTERS, 411, 3, 228, 232, Jan. 2007, [Peer-reviewed]
English, Scientific journal

SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes
Makiko Fujii, Lyudmila A. Lyakh, Cameron P. Bracken, Junya Fukuoka, Morisada Hayakawa, Tadasuke Tsukiyama, Steven J. Soil, Melissa Harris, Sonia Rocha, Kevin C. Roche, Shin-ichi Tominaga, Jin Jen, Neil D. Perkins, Robert J. Lechleider, Anita B. Roberts
MOLECULAR CELL, 24, 5, 771, 783, Dec. 2006, [Peer-reviewed]
English, Scientific journal

Wnt3a links left-right determination with segmentation and anteroposterior axis elongation
MA Nakaya, K Biris, T Tsukiyama, S Jaime, JA Rawls, TP Yamaguchi
DEVELOPMENT, 132, 24, 5425, 5436, Dec. 2005, [Peer-reviewed]
English, Scientific journal

Early embryonic death in mice lacking the beta-catenin-binding protein duplin
M Nishiyama, K Nakayama, R Tsunematsu, T Tsukiyama, A Kikuchi, KI Nakayama
MOLECULAR AND CELLULAR BIOLOGY, 24, 19, 8386, 8394, Oct. 2004, [Peer-reviewed]
English, Scientific journal

Increased proliferation of B cells and auto-immunity in mice lacking protein kinase C delta
A Miyamoto, K Nakayama, H Imaki, S Hirose, Y Jiang, M Abe, T Tsukiyama, H Nagahama, S Ohno, S Hatakeyama, KI Nakayama
NATURE, 416, 6883, 865, 869, Apr. 2002, [Peer-reviewed]
English, Scientific journal

Down-regulation of p27(Kip1) expression is required for development and function of T cells
T Tsukiyama, N Ishida, M Shirane, YA Minamishima, S Hatakeyama, M Kitagawa, K Nakayama, K Nakayama
JOURNAL OF IMMUNOLOGY, 166, 1, 304, 312, Jan. 2001, [Peer-reviewed]
English, Scientific journal

Development of dendritic epidermal T cells with a skewed diversity of gamma delta TCRs in V delta 1-deficient mice
H Hara, K Kishihara, G Matsuzaki, H Takimoto, T Tsukiyama, RE Tigelaar, K Nomoto
JOURNAL OF IMMUNOLOGY, 165, 7, 3695, 3705, Oct. 2000, [Peer-reviewed]
English, Scientific journal

Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde; in vitro analysis with liver subcellular fraction derived from human and Aldh2 gene targeting mouse
K Kitagawa, T Kawamoto, N Kunugita, T Tsukiyama, K Okamoto, A Yoshida, K Nakayama, K Nakayama
FEBS LETTERS, 476, 3, 306, 311, Jul. 2000, [Peer-reviewed]
English, Scientific journal

Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice
H Takai, K Tominaga, N Motoyama, YA Minamishima, H Nagahama, T Tsukiyama, K Ikeda, K Nakayama, N Nakanishi, K Nakayama
GENES & DEVELOPMENT, 14, 12, 1439, 1447, Jun. 2000, [Peer-reviewed]
English, Scientific journal

Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication
K Nakayama, H Nagahama, YA Minamishima, M Matsumoto, Nakamichi, I, K Kitagawa, M Shirane, R Tsunematsu, T Tsukiyama, N Ishida, M Kitagawa, K Nakayama, S Hatakeyama
EMBO JOURNAL, 19, 9, 2069, 2081, May 2000, [Peer-reviewed]
English, Scientific journal

Establishment of an embryonic stem (ES) cell line derived from a non-obese diabetic (NOD) mouse: in vivo differentiation into lymphocytes and potential for germ line transmission
S Nagafuchi, H Katsuta, K Kogawa, T Akashi, S Kondo, Y Sakai, T Tsukiyama, D Kitamura, Y Niho, T Watanabe
FEBS LETTERS, 455, 1-2, 101, 104, Jul. 1999, [Peer-reviewed]
English, Scientific journal

DNA-Liposome complexのマウス受精卵前核注入による外来遺伝子導入について
築山 忠維, 新谷 真美, 尾川 昭三
明治大学農学部研究報告, 113, 113, 17, 27, 明治大学農学部, Sep. 1997, [Peer-reviewed], [Lead author]
Japanese, Research institution

Investigation for functional recovery of oncogenic RNF43 mutants without Wnt receptor degradation
築山忠維, 畠山鎮次, 日本分子生物学会年会プログラム・要旨集(Web), 46th, 2023

Wnt/β-cateninシグナルが表皮角化細胞のヘミデスモソームを制御する　　　　　　　　　　　　　　　
小住 英之, 野原 拓馬, 藤村 悠, 岩田 浩明, 中村 秀樹, 氏家 英之, 夏賀 健, 渡邉 美佳, Donati Giacomo, 新熊 悟, 築山 忠維, 日本皮膚科学会雑誌, 132, 12, 2697, 2697, Nov. 2022
(公社)日本皮膚科学会, Japanese

Mutation in only 2 genes allows multi-step tumorigenesis.　　　　　　　　　　　　　　　
Tadasuke Tsukiyama, Tohru Ishitani, Shigetsugu Hatakeyama, CANCER SCIENCE, 112, 933, 933, Feb. 2021, [Lead author]

085 Type XVII collagen suppresses interfollicular epidermal proliferation in neonatal and aged skin, and helps rejuvenate epidermis
M. Watanabe, K. Natsuga, W. Nishie, G. Donati, Y. Fujimura, T. Tsukiyama, H. Ujiie, M. Ozaki, F.M. Watt, H. Shimizu, Journal of Investigative Dermatology, 137, 10, S207, S207, Oct. 2017
Elsevier BV

メディエーター複合体による転写終結制御機構
高橋秀尚, 柴田美音, 瀧川一学, 渡部昌, 築山忠維, 山本淳一, 山口雄輝, 藤井聡, 飯田緑, RANJAN Amol, SATO Shigeo, TOMOMORI‐SATO Chieri, CONAWAY Joan, CONAWAY Ronald, 畠山鎮次, 日本生化学会大会(Web), 90th, ROMBUNNO.4P2T15‐06(3P‐0635) (WEB ONLY), 0635)], 2017
生命科学系学会合同年次大会運営事務局, Japanese

ユビキチン化酵素RNF43によるWntシグナル制御とその破綻による発がん　　　　　　　　　　　　　　　
築山 忠維, 日本応用酵素協会誌, 52, 27, 33, 2017, [Invited]
Japanese, Introduction other

メディエーター複合体のサブユニットMED26はLittle elongation complexをリクルートすることでsnRNA遺伝子の転写を制御する　　　　　　　　　　　　　　　
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, 水島航, 林正康, 大川恭行, Joan, W. Conaway,Ronal, C. Conaway, 畠山鎮次, 北海道医学雑誌, 90, 1, 76, 76, 2015
Japanese

プロポロリスコーティング床敷はケージ内常在菌の増殖とマウスアレルゲンの発生を抑制する
TOSA NORIKO, YOSHIMATSU, KUMIKO, TSUKIYAMA TADAYUI, HATAKEYAMA SHIGETSUGU, ARIKAWA JIRO, 日本実験動物学会総会講演要旨集, 61st, 280, 01 May 2014
Japanese

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
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, 日本生化学会大会(Web), 87th, WEB ONLY 2T15P-16(3P-502), 16], 2014
(公社)日本生化学会, Japanese

メディエーター複合体による転写伸長制御
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 W, 築山忠維, 林正康, 大川恭行, CONAWAY Joan, CONAWAY Ronald C, 畠山鎮次, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 1W15-3(1P-0237) (WEB ONLY), 2014
Japanese

AN INFLAMMATORY CYTOKINE IL-1B IS INVOLVED IN BLADDER REMODELLING AFTER PARTIAL BLADDER OUTLET OBSTRUCTION IN MICE
Y. Kanno, T. Mitsui, T. Kitta, K. Moriya, T. Tsukiyama, S. Hatakeyama, K. Nonomura, NEUROUROLOGY AND URODYNAMICS, 32, 6, 925, 926, Aug. 2013
English, Summary international conference

ダイオキシン受容体内因性リガンドによる前立腺癌細胞におけるアンドロゲンレセプター発現低下と増殖抑制　　　　　　　　　　　　　　　
丸山覚, 築山忠維, 宮島直人, 土屋邦彦, 安部崇重, 佐澤陽, 篠原信雄, 畠山鎮次, 野々村克也, 日本泌尿器科学会雑誌, 104, 2, 415, Mar. 2013
Japanese

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
TAKAHASHI Hidehisa, 瀧川一学, ANWAR Delnur, 柴田美音, TOMOMORI‐SATO Chieri, SATO Shigeo, RANJAN Amol, SEIDEL Chris, 築山忠維, 渡部昌, 林正康, 大川恭行, CONAWAY Joan, CONAWAY Ronald, 畠山鎮次, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 1P-0182 (WEB ONLY), 2013
Japanese

Generation and analysis of thymocyte specific expressed p27^ transgenic mice
TSUKIYAMA Tadasuke, HATAKEYAMA Shigetsugu, KITAGAWA Masatoshi, NAKAYAMA Keiko, NAKAYAMA Kei-ichi, 日本分子生物学会年会プログラム・講演要旨集, 21, 589, 589, 01 Dec. 1998
Japanese

発がん過程におけるシグナルのクロストーク
築山忠維
北海道若手がん研究会（HYCIC), 03 Dec. 2024, Oral presentation
03 Dec. 2024 - 03 Dec. 2024, 42063426

発がん過程におけるシグナルのクロストーク
築山忠維
Wnt研究会2024, 30 Nov. 2024, Oral presentation
30 Nov. 2024 - 30 Nov. 2024, 42063426

発がん型RNF43変異体にWnt受容体分解機能を回復させるための検討
築山忠維
第47回日本分子生物学会年会, 28 Nov. 2024, Poster presentation
26 Nov. 2024 - 29 Nov. 2024, 42063426

代謝がWntシグナルに及ぼす影響の検討　　　　　　　　　　　　　　　
築山忠維
Wnt研究会, 09 Dec. 2023, Japanese, Oral presentation

Wnt受容体分解機能を失った発がん型RNF43変異体を機能回復させる試み
築山忠維, 畠山鎮次
第46回日本分子生物学会年会, 08 Dec. 2023, English, Poster presentation
42063426

発がん過程におけるWntシグナルからp53へのクロストーク
築山忠維, 畠山鎮次
第82回日本癌学会学術総会, 23 Sep. 2023, English, Oral presentation
42063426

Wnt receptor regulation and maintaining homeostasis
Tadasuke Tsukiyama
CGE International Seminar Series 2023, 27 Mar. 2023, English, Public discourse
09 Jan. 2023 - 22 May 2023, 24556193, [Invited]

多段階発がんにおけるRNF43遺伝子変異の意義
築山忠維
北海道がん若手研究者交流会, 17 Mar. 2023, Japanese, Oral presentation
17 Mar. 2023 - 17 Mar. 2023, 24556193, [Invited]

A role of RNF43 other than Wnt receptor regulation in oncogenesis (oral)
Tadasuke Tsukiyama
Wnt 2022, 18 Nov. 2022, English, Oral presentation
15 Nov. 2022 - 19 Nov. 2022, 24556193

A role of RNF43 other than Wnt receptor regulation in oncogenesis (poster)
Tadasuke Tsukiyama, Shigetsugu Hatakeyama
Wnt 2022, 17 Nov. 2022, English, Poster presentation
15 Nov. 2022 - 19 Nov. 2022, 24556193

Complex role of Wnt receptor regulation in multistep carcinogenesis
築山忠維, 畠山鎮次
第81回日本癌学会学術総会, 30 Sep. 2022, Japanese, Poster presentation
29 Sep. 2022 - 01 Oct. 2022, 24556193

Wnt受容体調節の破綻が多段階発がん過程で果たす複雑な役割　　　　　　　　　　　　　　　
築山忠維
第59回日本生化学会北海道支部例会, 09 Jul. 2022, Japanese, Nominated symposium
[Invited]

Wnt受容体の発現調節異常と発がん機構の解明　　　　　　　　　　　　　　　
築山忠維, 石谷太, 高橋秀尚, 松本雅記, 大場雄介, 中山敬一, Koo Bonkyoung, 畠山鎮次
第94回日本生化学会大会, 05 Nov. 2021, Japanese, Nominated symposium
[Invited]

Wnt receptor regulation
築山忠維
Wnt研究会2021, 14 Jan. 2021, Japanese, Oral presentation
24556193

単一遺伝子変異による多段階発がんの起動と完成　　　　　　　　　　　　　　　
築山忠維
第79回日本癌学会学術総会, 01 Oct. 2020, English, Others
01 Oct. 2020 - 03 Oct. 2020

RNF43の遺伝子変異は多段階発がんステップにおいてWntとp53経路の変異を代償する　　　　　　　　　　　　　　　
築山 忠維
第42回日本分子生物学会年会, 03 Dec. 2019, Japanese, Poster presentation
[Domestic Conference]

幹細胞特異的ユビキチンリガーゼRNF43の遺伝子変異による多段階発がんステップの起動と完成　　　　　　　　　　　　　　　
築山 忠維
第78回日本癌学会学術総会, 26 Sep. 2019, Japanese, Oral presentation
[Domestic Conference]

A broken tumor suppressor RNF43 is repaired by phosphorylation.　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第77回日本癌学会学術総会, 28 Sep. 2018, English, Oral presentation
[Domestic Conference]

Phosphorylation of RNF43 is an essential switch to suppress Wnt signalling a nd regulates embryonic development, stem cell maintenance and tumorigenesis.　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第91回日本生化学会大会, 25 Sep. 2018, Japanese, Oral presentation
[Domestic Conference]

RNF43のリン酸化によるWntシグナルの活性制御は個体の恒常性を制御する　　　　　　　　　　　　　　　
築山 忠維
Wnt研究会2017, 10 Dec. 2017, Japanese, Oral presentation
[Domestic Conference]

Aberrant Wnt signaling and tumorigenesis by RNF43 mutation in animal models　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
ConBio2017, 08 Dec. 2017, English, Oral presentation
[Domestic Conference]

Stem cell ubiquitin ligase RNF43 governs morphogenesis and tumorigenesis thorough Wnt signaling　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第76回日本癌学会学術総会, 28 Sep. 2017, Japanese, Public symposium
[Domestic Conference]

Diverse functions of Wnt signaling in our life　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第39回日本分子生物学会年会, 30 Nov. 2016, English, Public symposium
[Invited], [Domestic Conference]

Post-translational modification of RNF43; a molecular switch of Wnt signaling　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第39回日本分子生物学会年会, 30 Nov. 2016, English, Invited oral presentation
[Invited], [Domestic Conference]

RNF43の翻訳後修飾はWntシグナル調節のスイッチとして機能する　　　　　　　　　　　　　　　
築山 忠維
第75回日本癌学会学術総会, 07 Oct. 2016, English, Oral presentation
[Domestic Conference]

Post-translational modification of RNF43; a molecular switch of Wnt signaling　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
Wnt meeting 2016, 15 Sep. 2016, English
[International presentation]

カエルモデルを用いたRNF43のリン酸化によるWntシグナル調節機構の解明　　　　　　　　　　　　　　　
築山 忠維
平成27年度「個体レベルでのがん研究支援活動」ワークショップ, 04 Feb. 2016, Japanese
[Domestic Conference]

カエルモデルを用いたRNF43のWntシグナル調節と発がんにおける機能検討　　　　　　　　　　　　　　　
築山 忠維
第74回日本癌学会学術総会, 08 Oct. 2015, Japanese, Oral presentation
[Domestic Conference]

カエルモデルから明らかになったWntシグナル調節とがんにおけるRNF43の機能　　　　　　　　　　　　　　　
築山 忠維
日本生化学会北海道支部 第52回支部例会, 17 Jul. 2015, Japanese, Oral presentation
[Domestic Conference]

Missense mutations of RNF43 establish a positive feedback loop of Wnt/βcatenin signaling　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
2015「個体レベルでのがん研究支援活動」ワークショップ, 05 Feb. 2015, Japanese, Oral presentation
[Domestic Conference]

Missense mutations of RNF43 establish a positive feedback loop of Wnt/βcatenin signaling　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第37回日本分子生物学会年会, 27 Nov. 2014, Japanese, Poster presentation
[Domestic Conference]

RNF43のミスセンス変異はWnt/βcateninシグナルの正のフィードバックループを形成する　　　　　　　　　　　　　　　
築山 忠維
第73回日本癌学会年会, 27 Sep. 2014, Japanese, Oral presentation
[Domestic Conference]

RNF43遺伝子のミスセンス変異によるWnt/βcatenin経路のポジティブフィードバックループ形成　　　　　　　　　　　　　　　
築山 忠維
日本生化学会北海道支部 第51回支部例会, 18 Jul. 2014, Japanese, Oral presentation
[Domestic Conference]

Missense mutations convert RNF43 tumour suppressor into an oncogene　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第36回日本分子生物学会年会, 03 Dec. 2013, English, Poster presentation
[Domestic Conference]

RNF43 negatively regulates Wnt/beta-catenin and noncanonical Wnt signallin g pathways through distinct mechanisms　　　　　　　　　　　　　　　
Tadasuke Tsukiyama
第72回日本癌学会学術総会, 04 Oct. 2013, English, Oral presentation
[Domestic Conference]

RNF43はcanonical/noncanonical Wntシグナルの両方を抑制する　　　　　　　　　　　　　　　
築山 忠維
第35回日本分子生物学会年会, 11 Dec. 2012, English, Poster presentation
マリンメッセ福岡・福岡, [Domestic Conference]

RNF43はNEDL1と結合し、p53依存性の転写を調節する　　　　　　　　　　　　　　　
築山 忠維
第71回日本癌学会学術総会, 19 Sep. 2012, English, Poster presentation
札幌, [Domestic Conference]

Ymer functions as a multifunctional regulator in NF-kB and Fas signaling pathways.　　　　　　　　　　　　　　　
築山 忠維
41st Australasian Society for Immunology Annual Meeting, 13 Dec. 2011, English, Oral presentation
アデレード･オーストラリア, [International presentation]

ポリユビキチン結合タンパク質Ymer は 炎症反応を抑制する　　　　　　　　　　　　　　　
築山 忠維
第48回日本生化学会北海道支部例会, 05 Aug. 2011, Japanese, Oral presentation
札幌, [Domestic Conference]

Ymerトランスジェニックマウスの解析　　　　　　　　　　　　　　　
築山 忠維
第32回日本分子生物学会年会, 09 Dec. 2009, Japanese, Poster presentation
[Domestic Conference]

がん抑制遺伝子としてのWnt5a　　　　　　　　　　　　　　　
築山 忠維
Wntシグナルシンポジウム, 24 Mar. 2009, Japanese, Invited oral presentation
[Invited], [Domestic Conference]

K63-ポリユビキチン鎖を介してNF-kBシグナルを抑制するYmerの機能解析　　　　　　　　　　　　　　　
築山 忠維
第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会 （BMB2008）, 09 Dec. 2008, Japanese, Oral presentation
[Domestic Conference]

改良型NF-κB活性検出システムの構築　　　　　　　　　　　　　　　
築山 忠維
第73回日本インターフェロン・サイトカイン学会学術集会, 11 Jul. 2008, Japanese, Poster presentation
[Domestic Conference]

改良型NF-kB活性検出システムの構築　　　　　　　　　　　　　　　
築山 忠維
第30回日本分子生物学会年会・第80回日本生化学会大会 合同大会 （BMB2007）, 11 Dec. 2007, Japanese, Poster presentation
[Domestic Conference]

Wnt5a is a haploinsufficient tumor suppressor that cooperates with Tcf1 to suppress T cell lymphomas　　　　　　　　　　　　　　　
築山 忠維
20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress, 22 Jun. 2006, English, Poster presentation
[International presentation]

Wnt5a synergizes with Tcf1 to suppress T-cell lymphoma　　　　　　　　　　　　　　　
築山 忠維
日本分子生物学会年会, 10 Dec. 2004, Japanese, Oral presentation
[Domestic Conference]

Evidence that Wnt5a functions as a tumor suppressor in T-cell lymphoma　　　　　　　　　　　　　　　
築山 忠維
Cold Spring Harboer-Mouse molecular Genetics meeting, 03 Sep. 2004, English, Poster presentation
[International presentation]

Wnt5a is a tumor suppressor in T-cell lymphoma　　　　　　　　　　　　　　　
築山 忠維
Wnt meeting, 22 May 2004, Japanese, Oral presentation
[International presentation]

Wnt signaling regulates mammalian body plan and tumorigenesis.　　　　　　　　　　　　　　　
築山 忠維
NCI retreat, 22 Oct. 2003, English, Oral presentation
[Domestic Conference]

Wnt signaling pathway and anterior- posterior body axis formation　　　　　　　　　　　　　　　
築山 忠維
Society for Developmental Biology Annual Meeting, 03 Aug. 2003, English, Poster presentation
[International presentation]

Downregulation of p27Kip1 is required for T cell development　　　　　　　　　　　　　　　
築山 忠維
Cold Spring Harbor Laboratory-The cell cycle meeting, 18 May 2000, English, Poster presentation
[International presentation]

T細胞の分化と細胞周期：p27Kip1トランスジェニックマウスの解析　　　　　　　　　　　　　　　
築山 忠維
日本分子生物学会年会, 09 Dec. 1999, Japanese, Poster presentation
[Domestic Conference]

胸腺細胞特異的発現p27Kip1トランスジェニックマウスの作製と解析　　　　　　　　　　　　　　　
築山 忠維
日本分子生物学会年会, 19 Dec. 1998, Japanese, Poster presentation
[Domestic Conference]

DNA-リポソームcomplexの前核注入によるTgマウス胚の作出　　　　　　　　　　　　　　　
築山 忠維
日本繁殖学会, 01 Oct. 1996, Japanese, Oral presentation
[Domestic Conference]

DNA-リポソームcomplexの前核注入によるTgマウス胚の作出　　　　　　　　　　　　　　　
築山 忠維
日本畜産学会, 28 Mar. 1996, Japanese, Oral presentation
[Domestic Conference]

生化学実習　　　　　　　　　　　　　　　
北海道大学

プレメディカル演習　　　　　　　　　　　　　　　
北海道大学

基盤医学研究 I・II　　　　　　　　　　　　　　　
北海道大学

医学総論　　　　　　　　　　　　　　　
北海道大学

基本医学研究 I・II　　　　　　　　　　　　　　　
北海道大学

基本医学総論　　　　　　　　　　　　　　　
北海道大学

医学研究セミナー　　　　　　　　　　　　　　　
北海道大学

家畜繁殖学実習　　　　　　　　　　　　　　　
明治大学農学部

医学研究演習　　　　　　　　　　　　　　　
北海道大学

基礎医学実習　　　　　　　　　　　　　　　
北海道大学

2018 - Present
日本生化学会　　　　　　　　　　　　　　　

Nov. 2016 - Present
Wnt研究会　　　　　　　　　　　　　　　

Mar. 2012 - Present
日本癌学会　　　　　　　　　　　　　　　

Aug. 1998 - Present
THE MOLECULAR BIOLOGY SOCIETY OF JAPAN　　　　　　　　　　　　　　　

発がん過程におけるRNF43をハブとしたWntシグナルとp53経路のクロストーク機構の解明（継続）　　　　　　　　　　　　　　　
東京大学医科学研究所共同研究
Apr. 2025 - Mar. 2026
東京大学, 東京大学医科学研究所, Principal investigator

多段階発がんにおけるWntシグナルからp53経路へのクロストークの解明と治療応用
科学研究費助成事業 基盤研究(C)
Apr. 2023 - Mar. 2026
築山 忠維
日本学術振興会, 基盤研究(C), 北海道大学, 23K06605

発がん過程におけるRNF43をハブとしたWntシグナルとp53経路のクロストーク機構の解明　　　　　　　　　　　　　　　
東京大学医科学研究所共同研究
Apr. 2023 - Mar. 2025
築山忠維
東京大学医科学研究所, Principal investigator

RNF43の遺伝子変異を標的とした新たながん治療法の開発（継続）　　　　　　　　　　　　　　　
金沢大学がん進展制御研究所 共同利用・共同研究
Apr. 2023 - Mar. 2024
築山忠維
金沢大学がん進展制御研究所, Principal investigator

RNF43の遺伝子変異を標的とした新たながん治療法の開発　　　　　　　　　　　　　　　
令和４年度 共同研究
Apr. 2022 - Mar. 2023
金沢大学がん進展制御研究所, Principal investigator

Wnt受容体の発現調節破綻による発がん機構の解明をがん治療に応用する ための基礎的研究　　　　　　　　　　　　　　　
ビジョナリーリサーチ助成
Apr. 2021 - Mar. 2023
公益財団法人 武田科学振興財団, Principal investigator

RNF43によるWnt受容体ユビキチン化の分子メカニズムの解明と治療への応用
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2019 - Mar. 2022
築山 忠維
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 19K07633

糖代謝が個体の恒常性維持に関与するメカニズムの解明　　　　　　　　　　　　　　　
内分泌・代謝学共同研究拠点 共同研究
Apr. 2020 - Mar. 2021
群馬大学, 群馬大学生体調節研究所

Wntシグナル調節因子が代謝変化を通して発がんに関与するメカニズムの解明　　　　　　　　　　　　　　　
大阪大学微生物病研究所共同研究課題
Apr. 2020 - Mar. 2021
大阪大学, 大阪大学微生物病研究所, Principal investigator

糖代謝がWntシグナルによる恒常性維持に及ぼす影響の検討　　　　　　　　　　　　　　　
生体・調節研究所内分泌 代謝学共同研究拠点共同研究
Apr. 2019 - Mar. 2020
群馬大学, 群馬大学, Principal investigator

The function of RNF43 in tumorigenesis and maintaining homeostasis
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2016 - Mar. 2020
Tsukiyama Tadasuke
We show in this research that;
1, CK1 phosphorylates RNF43 on multiple serines. 2, Phosphorylation activates ubiquitinating function of RNF43. 3, Mutation of RNF43 in these serines induces the excess of Wnt signaling. 4, Such mutations do not change the function of RNF43 in suppression of p53-dependent cellular reactions.
These results suggest that mutations in serine on RNF43 act concurrently in the first step: Wnt activation and in the 3rd step: p53 inactivation. Furthermore, we propose a new model of tumorigenesis: two mutations, in RNF43 and Ras, is sufficient for the onset of tumor.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 16K07105

Wntシグナルが恒常性維持に果たす役割のゼブラフィッシュモデルを用いた解明　　　　　　　　　　　　　　　
生体・調節研究所内分泌 代謝学共同研究拠点共同研究
Apr. 2018 - Mar. 2019
群馬大学, 群馬大学, Principal investigator

ユビキチン化酵素RNF43による発がん制御機構の解明　　　　　　　　　　　　　　　
酵素研究助成
Sep. 2016 - Aug. 2017
築山 忠維
公益財団法人 日本応用酵素協会, Principal investigator, Competitive research funding

ゼブラフィッシュモデルを用いたRNF43の機能解析　　　　　　　　　　　　　　　
生体防御医学研究所 発生工学共同研究課題
Apr. 2016 - Mar. 2017
九州大学, 九州大学生体防御医学研究所, Principal investigator

Wntシグナル調節メカニズムの解明と膵臓がんの診断治療への応用　　　　　　　　　　　　　　　
膵臓病研究奨励賞
Oct. 2015 - Oct. 2016
築山 忠維
公益財団法人 日本膵臓病研究財団, Principal investigator, Competitive research funding

Molecular role of RNF43 in Wnt signaling and tumorigenesis
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2013 - Mar. 2016
Tsukiyama Tadasuke, Hatakeyama Shigetsugu, Takahashi Hidehisa
Wnt signaling pathways are tightly regulated by ubiquitination of their signal transducers and dysregulation of these pathways promotes the tumorigenesis. It has been reported that an ubiquitin ligase RNF43 plays important role in the Fzd-dependent regulation of Wnt signaling pathways. We recently reported that N-terminal of RNF43 is indespensable to regulate Fzd-dependent suppression of Wnt signaling pathways although C-terminal of RNF43 is able to inhibit noncanonical Wnt signaling in a Fzd-independent but Dvl-dependent fashion. In addition missense mutations found in cancer patients convert the function of RNF43 to the positive regulator of Wnt/βcatenin signaling and establish a positive feedback loop of Wnt/βcatenin signaling to accelerate tumorigenesis. These results have been published in a scientific journal [ Tsukiyama, MCB, 35:2007 (2015)].
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 25430102

Comprehensive analysis of TRIM type ubiquitin ligases in cell proliferation and differentiation
Grants-in-Aid for Scientific Research
01 Apr. 2012 - 31 Mar. 2015
HATAKEYAMA Shigetsugu, TSUKIYAMA Tadasuke, TAKAHASHI Hidehisa
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.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 24390065

Comprehensive analysis of the regulation of carcinogenesis through TRIM type ubiquitin ligases
Grants-in-Aid for Scientific Research
2009 - 2011
HATAKEYAMA Shigetsugu, OKUMURA Fumihiko, TSUKIYAMA Tadasuke
Ubiquitination is one of the posttranslational modifications used by eukaryotic cells, and the ubiquitin-mediated proteolytic pathway plays a crucial role in the elimination of short-lived regulatory proteins. Members of the family of tripartite motif (TRIM)-containing proteins are idefined as E3 ubiquitin ligases. There are now more than 70 known TRIM proteins in humans and mice. In this study, we analyzed the relationship between TRIM proteins and cancinogenesis.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 21390087

Establishment and application of the library for in vivo imaging in living mice.
Grants-in-Aid for Scientific Research(若手研究(B))
Apr. 2008 - Mar. 2010
Tadasuke TSUKIYAMA
We have established and reported for cNAT system, which can detect the activity of NF-κB signaling. Next, we generated cNAT reporter transgenic mice and cNotch reporter system/transgenic mice to detect NF-κB signaling and Notch signaling respectively, in living mice.
Ministry of Education, Culture, Sports, Science and Technology, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 20700361

マウス生体内におけるシグナル経路のin vivo イメ ージングシステムの確立と応用　　　　　　　　　　　　　　　
生命科学研究助成金
Apr. 2007 - Mar. 2008
築山 忠維
秋山財団, Principal investigator, Competitive research funding

マウス生体内におけるシグナル経路のin vivoイメージングシステムの確立と応用
科学研究費補助金・若手研究(B)
Apr. 2006 - Mar. 2008
築山 忠維
全ての生物においてシグナル伝達システムの厳密な制御は、生命を維持することに決定的に重要である。我々は、本研究において生体内でこれらのシグナル活性を蛍光・発光によりイメージングするためのシステム構築を目指し、様々なシグナル活性変化を検出するレポーターとして活用することで、個体の形態形成から恒常性維持までに至る生命現象を対象とした幅広い研究に対応させることを目的とした。まず我々はガン、免疫異常、炎症などの多くの疾患に重要な役割を果たすNF-kBシグナルに注目し、その活性を検出するためのシステム構築を行った。NF-kBシグナルを高感度・特異的に検出するレポーターシステムの確立には、NF-kB結合配列とNF-kBシグナルの下流において特異的と考えられるIL-2遺伝子由来ミニマルプロモーターを用い、改良型NF-kBレポーター:NATシステムを構築した。さらにシグナルの蓄積とリアルタイムでのシグナル活性変化検出ため、レポーター遺伝子として安定型・不安定型のルシフェラーゼ・EGFPと組み合わせ細胞レベルでの検討を行った結果、従来のNF-kBシグナルレポーターシステムに対し検出感度で18倍、特異性で5倍高い値を示し、またシグナルの蓄積とリアルタイムでのシグナル活性変化を同時に測定出来るシステムであることが示された(Matsuda et al., Immunology Letters、 200...
日本学術振興会, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 18700393

Comprehensive analysis of TRIM family ubiquitin ligases
Grants-in-Aid for Scientific Research(基盤研究(B))
2006 - 2007
Shigetsugu HATAKEYAMA, 築山 忠維
Ubiquitination is a versatile post-translational modification mechanism used by eukaryotic cells mainly to control protein levels through proteasome-mediated proteolysis. Ubiquitin conjugation is achieved by several enzymes that act in concert, a ubiquitin-protein ligase (E3). E3 is thought to be the component of the ubiquitin conjugation system that is most directly responsible for substrate recognition. Enzymes belonging to class E3 that have so far been identified include members of the HECT (homologous to E6-AP carboxyl terminus), RING-finger and U-box families of proteins. So far; we h...
Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 18390079

ハイブリッド型ユビキチン化酵素による神経変性疾患の治療
科学研究費補助金(萌芽研究)
2006 - 2007
畠山 鎮次, 築山 忠維
多くの細胞質・核質に存在するタンパク質の分解に関わっているのはユビキチン-プロテアソーム系である。この分解系の特徴は、基質特異性が高く、分解速度が速いことである。分解されるべきタンパク質はユビキチンが鎖状に結合され(ポリユビキチン鎖)、タンパク質分解装置であるプロテアソームがポリユビキチン鎖を認識して標的タンパク質ごと分解する。標的タンパク質のユビキチン化に必要な酵素群の中で、特にユビキチンリガーゼは標的タンパク質を認識し、最終的にユビキチンを付加する重要な因子である。本研究課題においては、各ポリグルタミン病関連タンパク質(ハンチンティン、Atrophin-1、Ataxin(ATX)-1,-2,-3,-17等)には特異的に結合するタンパク質が同定されているので、この結合タンパク質とユビキチンリガーゼであるU-ボックスタンパク質のキメラ酵素(人工ハイブリッドユビキチンリガーゼ)を作製し、ポリグルタミン含有タンパク質が人工ハイブリッドユビキチンリガーゼによってユビキチン化を受け、プロテアソームによって分解される系を構築する。さらに実際の遺伝子治療に応用できるかどうかを検討するために、ウイルスベクターを利用して細胞やマウスへの導入実験を行い、神経機能異常に対する効果を判定する。特に、ATX-3/MJD1とVCP/p97の結合に注目し、VCPにおける最小結合領域を同定しているところで...
文部科学省, 萌芽研究, 北海道大学, Coinvestigator not use grants, Competitive research funding, 18659252

大腸がんの進行抑制できるタンパク質の働きを初解明　　　　　　　　　　　　　　　
13 Oct. 2020
Other than myself
NHK
北海道のがん研究最前線・ほっとニュース北海道
[Media report]

大腸がん発症のスイッチを発見 北大　　　　　　　　　　　　　　　
09 Oct. 2020
Other than myself
東京メトロポリタンテレビジョン
MEDICAL NEWS LINE
[Media report]

大腸がん発症、RNF43遺伝子のリン酸化が 関わる新たなメカニズムを発見－北大ほか
18 Sep. 2020
Other than myself
QlifePro
医療NEWS
http://www.qlifepro.com/news/20200917/rnf43-tumorigenesis.html, 24556193, [Internet]

〔Major achievements〕大腸がんタンパク質の働き解明
18 Sep. 2020
Other than myself
NHK
NHKニュース・おはよう北海道
24556193, [Media report]

Molecular basis underlying colorectal cancer revealed　　　　　　　　　　　　　　　
15 Sep. 2020
bioengineer.org
Bioengineer
https://bioengineer.org/molecular-basis-underlying-colorectal-cancer-revealed/, [Internet]

Molecular basis underlying colorectal cancer revealed　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
7thspace.com
7thSpace
http://7thspace.com/headlines/1309965/molecular_basis_underlying_colorectal_cancer_revealed.html, [Internet]

The Wnt pathway gets even more complicated　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
American Association for the Advancement of Science (AAAS)
EurekAlart!
https://www.eurekalert.org/pub_releases/2020-09/iiom-twp091520.php, [Internet]

Molecular basis underlying colorectal cancer revealed　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
bionewscentral.com
BioNews CENTRAL
https://bionewscentral.com/molecular-basis-underlying-colorectal-cancer-revealed/, [Internet]

The Wnt pathway gets even more complicated　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
alphagalileo.org
Alpha Galileo
https://www.alphagalileo.org/en-gb/Item-Display/ItemId/197278?returnurl=https://www.alphagalileo.org/en-gb/Item-Display/ItemId/197278, [Internet]

Molecular basis underlying colorectal cancer revealed by Hokkaido University　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
Oncology & Cancer
medicalxpress.com
https://medicalxpress.com/news/2020-09-molecular-basis-underlying-colorectal-cancer.html, [Internet]

Molecular basis underlying colorectal cancer revealed　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
asiaresearchnews.com
Asia Research News
https://www.asiaresearchnews.com/content/molecular-basis-underlying-colorectal-cancer-revealed, [Internet]

Scientists unravel the molecular mechanism underlying the causes of colorectal cancer　　　　　　　　　　　　　　　
15 Sep. 2020
Other than myself
news-medical.net
The Medical News
https://www.news-medical.net/news/20200915/Scientists-unravel-the-molecular-mechanism-underlying-the-causes-of-colorectal-cancer.aspx, [Internet]