Molecular and temporal-spatial regulation of ubiquitin ligase , F-box protein

• Project/Area Number: 20370076
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: NAKAYAMA Keiko Tohoku University, 大学院・医学系研究科, 教授 (60294972)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Noriko 東北大学, 大学院・医学系研究科, 助教 (10361073) ; FUNAYAMA Ryo 東北大学, 大学院・医学系研究科, 助教 (20452295) ; NAKANO Seiji 東北大学, 大学院・医学系研究科, 助手 (00529448) ; DEL CARPIO Munoz Carlos Adriel 東北大学, 大学院・工学研究科, 准教授 (20231053) ; NISHIDA Yuichiro 東北大学, 大学院・医学系研究科, 助教 (00551821) ; 山田 秀俊 東北大学, 大学院・医学系研究科, 助手 (70511955)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000); Fiscal Year 2010: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2009: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2008: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: ユビキチンリガーゼ / β-TrCP1 / Fbxw7 / ノックアウトマウス / ES細胞 / β-TcP2

Research Abstract

F-box protein functions as a ubiquitin ligase constructing SCF protein complex. In this preject, I focused my interest on typical F-box proteins, Fbxw7 and β-TrCP. I analyzed their gene targeting mice to elucidate the biological function of these proteins. Although Fbxw7 suppressed tumorigenesis in T lymphocytes and hematopoietic stem cell, it facilitated cell proliferation in primary embryonic fibroblasts and keratinocytes. b-TrCP promoted cell proliferation.

Research Products

• [Journal Article] Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. (2011)
  • Author(s): Onoyama, I., A.Suzuki, A.Matsumoto, K.Tomita, H.Katagiri, Y.Oike, K.Nakayama, K.I.Nakayama
  • Journal Title: J Clin Invest 121 Pages: 342-354
• [Journal Article] Fbxw7beta resides in the endoplasmic reticulum membrane and protects cells from oxidative stress. (2011)
  • Author(s): Matsumoto, A., Y.Tateishi, I.Onoyama, Y.Okita, K.Nakayama, K.I.Nakayama
  • Journal Title: Cancer Sci 102 Pages: 749-755
• [Journal Article] Localization of SMAP2 to the TGN and its Function in the Regulation of TGN Protein Transport. (2011)
  • Author(s): Funaki, T., S.Kon, R.E.Ronn, Y.Henmi, Y.Kobayashi, T.Watanabe, K.Nakayama, K.Tanabe, M.Satake
  • Journal Title: Cell Struct Funct 36 Pages: 83-95
  • NAID: 130004137566
• [Journal Article] Impaired ovarian development and reduced fertility in female mice deficient in Skp2. (2011)
  • Author(s): Fotovati, A., S.Abu-Ali, K.Nakayama, K.I.Nakayama
  • Journal Title: J Anat 218 Pages: 668-677
• [Journal Article] Fbxw7β resides in the endoplasmic reticulum membrane and protects cells from oxidative stress. (2011)
  • Author(s): Matsumot A, Tateishi Y, Onoyama I, Okita Y, Nakayama K, Nakayama KI
  • Journal Title: Cancer Sci. Volume: 102 Pages: 749-755
  • NAID: 10029292153
  • Peer Reviewed
• [Journal Article] Localization of SMAP2 to the TGN and its Function in the Regulation of TGN Protein Transport. (2011)
  • Author(s): Funaki T, Kon S, Ronn RE, Ilenmi Y, Watanabe T, Nakayama K, Tanabe K, Satake M
  • Journal Title: Cell Struct Funct. Volume: 36 Pages: 83-95
  • NAID: 130004137566
  • Peer Reviewed
• [Journal Article] Impaired ovarian development and reduced fertility in female mice defic ient in Skp2. (2011)
  • Author(s): Fotovati A, Abu-Ali S, Nakayama K, Nakayama KI
  • Journal Title: J Anat.
  • Peer Reviewed
• [Journal Article] Deleted in Esophageal Cancer 1(DEC1) is down-regulated and contribut es to migration in head and neck squamous cell carcinoma cell lines. (2011)
  • Author(s): Kunimoto Y, Kakano S, Kataoka H, Shimada Y, Oshimmura M, Kitanu H
  • Journal Title: ORL J Otorhinolarygol Relat Spec Volume: 73 Pages: 17-23
  • Peer Reviewed
• [Journal Article] Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/-mice. (2010)
  • Author(s): Wang, H., F.Bauzon, P.Ji, X.Xu, D.Sun, J.Locker, R.S.Sellers, K.Nakayama, K.I.Nakayama, D.CobrinikL. Zhu
  • Journal Title: Nat Genet 42 Pages: 83-88
• [Journal Article] Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. (2010)
  • Author(s): Tsuchiya, Y., T.Asano, K.Nakayama, T.Kato, Jr., M.Karin, H.Kamata
  • Journal Title: Mol Cell 39 Pages: 570-582
• [Journal Article] Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts. (2010)
  • Author(s): Masuda, K., Y.Ishikawa, I.Onoyama, M.Unno, I.M. de Alboran, K.I., Nakayama, K.Nakavama
  • Journal Title: Oncogene 29 Pages: 1798-1809
• [Journal Article] Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. (2010)
  • Author(s): Tsuchiya Y. Asano T, Nakayama K, Kato T Jr, Karin M, Kamata H
  • Journal Title: Mol Cell. Volume: 39 Pages: 570-582
  • Peer Reviewed
• [Journal Article] Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver (2010)
  • Author(s): Onoyama I, Suzuki A, Matsumoto A, Tbmita K, Katagiri H, Oike Y, Nakayama K, Nakayama Ki
  • Journal Title: J Clin Invest. Volume: 121 Pages: 342-354
  • Peer Reviewed
• [Journal Article] Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. (2010)
  • Author(s): Wang H, Bauzon F, Ji P, Xu X, Sun D, Locker J, Sellers RS, Nakayama K, Nakayama KI, Cobrinik D, Zhu L
  • Journal Title: Nat Genet 42 Pages: 83-88
  • Peer Reviewed
• [Journal Article] S-phase kinase-associated protein-2 (Skp2) promotes vascular smooth muscle cell proliferation and neointima formation in vivo. (2009)
  • Author(s): Wu, Y.J., G.B.Sala-Newby, K.T.Shu, H.I.Yeh, K.I.Nakayama, K.Nakayama, A.C.Newby, M.Bond
  • Journal Title: J Vase Surg 50 Pages: 1135-1142
• [Journal Article] Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model. (2009)
  • Author(s): Susaki, E., K.Nakayama, L.Yamasaki, K.I.Nakayama
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 5192-5197
• [Journal Article] Human synovial sarcoma proto-oncogene Syt is essential for early embryonic development through the regulation of cell migration. (2009)
  • Author(s): Kimura, T., M.Sakai, K.Tabu, L.Wang, R.Tsunematsu, M.Tsuda, H.Sawa, K.Nagashima, H.Nishihara, S.Hatakeyama, K.Nakayama, M.Ladanyi, S.Tanaka, K.I.Nakayama
  • Journal Title: Lab Invest 89 Pages: 645-656
• [Journal Article] Mechanoregulation of proliferation. (2009)
  • Author(s): Jiang, X., P.F.Austin, R.A.Niederhoff, S.R.Manson, J.J.Riehm, B.L.Cook, G.Pengue, K.Chitaley, K.Nakayama, K.I.Nakayama, S.J.Weintraub
  • Journal Title: Mol Cell Biol 29 Pages: 5104-5114
• [Journal Article] Protein kinase C[delta] differentially regulates platelet functional responses. (2009)
  • Author(s): Chari, R., T.Getz, B.Nagy, Jr., K.Bhavaraju, Y.Mao, Y.S.Bynagari, S.Murugappan, K.Nakayama, S.P.Kunapuli
  • Journal Title: Arterioscler Thromb Vasc Biol 29 Pages: 699-705
• [Journal Article] S-phase kinase-associated protein-2(Skp2)promotes vascular smooth muscle cell proliferation and neointima formation in vivo. (2009)
  • Author(s): Wu YJ, Sala-Newby GB, Shu KT, Yeh HI, Nakayama KI, Nakayama K, Newby AC, Bond M
  • Journal Title: J Vasc Surg. 50 Pages: 1135-1142
  • Peer Reviewed
• [Journal Article] Mechanoregulation of proliferation. (2009)
  • Author(s): Jiang X, Austin PF, Niederhoff RA, Manson SR, Riehm JJ, Cook BL, Pengue G, Chitaley K, Nakayama K, Nakayama KI, Weintraub SJ
  • Journal Title: Mol Cell Biol 18 Pages: 5104-5114
  • Peer Reviewed
• [Journal Article] Human synovial sarcoma proto-oncogene Syt is essential for early embryonic development through the regulation of cell migration. (2009)
  • Author(s): Kimura T, Sakai M, Tabu K, Wang L, Tsunematsu R, Tsuda M, Sawa H, Nagashima K, Nishihara H, Hatakeyama S, Nakayama K, Ladanyi M, Tanaka S, Nakayama KI
  • Journal Title: Lab Invest 89 Pages: 645-656
  • Peer Reviewed
• [Journal Article] Protein kinase C[delta]differentially regulates platelet functional responses. (2009)
  • Author(s): Chari R, Getz T, Nagy B Jr, Bhavaraju K, Mao Y, Bynagari YS, Murugappan S, Nakayama K, Kunapuli SP
  • Journal Title: Arterioscler Thromb Vasc Biol. 29 Pages: 699-705
  • Peer Reviewed
• [Journal Article] Complex regulation of cell-cycle inhibitors by Fbxw7 in mouse embryonic fibroblasts (2009)
  • Author(s): Masuda K, Ishikawa Y, Onoyama I, Unno M, de Alboran IM, Nakayama KI, Nakayama K
  • Journal Title: Oncogene 29 Pages: 1798-1809
  • Peer Reviewed
• [Journal Article] Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model (2009)
  • Author(s): E. Susaki, et.al
  • Journal Title: Proc. Natl. Acad. Sci. USA 106 Pages: 5192-5197
  • Peer Reviewed
• [Journal Article] Skp2 regulates the antiproliferative function of the tumor suppressor RASSFIA via ubiduitin-mediated degradation at the G1-S transition (2008)
  • Author(s): M.S. Song, et.al.
  • Journal Title: Oncogene 27 Pages: 3176-3185
  • Peer Reviewed
• [Journal Article] The Role ofβ-TrCP1 andβ-TrCP2 in Circadian Rhythm Generation by Mediating degradation of Clock Protein PER2 (2008)
  • Author(s): K. Ohsaki, et.al.
  • Journal Title: J. Biochem. 144 Pages: 609-618
  • Peer Reviewed
• [Journal Article] A functional link between Wnt signaling and SKP2-independent p27 turnover in mammary tumors (2008)
  • Author(s): G. A. Miranda-Carboni, et.al.
  • Journal Title: Genes Dev. 22 Pages: 3121-3134
  • Peer Reviewed
• [Journal Article] Notch-dependent cell cycle arrest and apoptosis in mouse embryonic fibroblasts lacking Fbxw7 (2008)
  • Author(s): Y. Ishikawa, et.al.
  • Journal Title: Oncogene 27 Pages: 6164-6174
  • Peer Reviewed
• [Journal Article] Targeting the p27 E3 ligase SCF(Skp2) results in p27-and Skp2-mediated cell-cycle arrest and activation of autophagy (2008)
  • Author(s): Q. Chen, et.al.
  • Journal Title: Blood 111 Pages: 4690-4699
  • Peer Reviewed
• [Presentation] Winter Camp of GCOE 2011 ～The Cultivation of New Generation of Scientists～ Tohoku University Global COE for Conquest of Singal Transcuction Dieseases with "Network Medicine" (2011)
  • Author(s): 西田有一郎
  • Organizer: Genome-wide comprehensive and comparative analysis of next-generation sequencing data between ChIP-seq and RNA-seq
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-05
• [Presentation] Winter Camp of GCOE 2011 ～The Cultivation of New Generation of Scientists～ Tohoku University Global COE for Conquest of Singal Transcuction Dieseases with "Network Medicine" (2011)
  • Author(s): 中野星児, 佐々木陽丞, 本橋ほずみ, 中山啓子
  • Organizer: Geminin deletion in hematopoietic stem cells promotes differentiation of megakaryocytes and platelets
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-05
• [Presentation] Winter Camp of GCOE 2011 ～The Cultivation of New Generation of Scientists～ Tohoku University Global COE for Conquest of Singal Transcuction Dieseases with "Network Medicine" (2011)
  • Author(s): 細金正樹, 舟山亮, 西田有一郎, 中山啓子
  • Organizer: Ras-mediated regional silencing around Fas gene locus
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-05
• [Presentation] Ras-mediated regional silencing around Fas gene locus. (2011)
  • Author(s): Masaki Hosogane, Ryo Funayama, Yuichiro Nishida, Keiko Nakavama
  • Organizer: 東北大学グローバルCOE Network Medicine創生拠点冬の合宿2011
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-05
• [Presentation] Geminin deletion in hematopoietic stem cells promotes differentiation of megakaryocytes and platelets. (2011)
  • Author(s): Seiji Nakano, Yousuke Sasaki, Hozumi Motohashi, Keiko Nakayama
  • Organizer: 東北大学グローバルCOE Network Medicine創生拠点冬の合宿2011
  • Place of Presentation: 仙台
  • Year and Date: 2011-02-05
• [Presentation] 第33回分子生物学会年会・第83回日本生化学会大会合同大会 (2010)
  • Author(s): 中野星児, 佐々木陽丞, 本橋ほずみ, 中山啓子
  • Organizer: Gemininは造血幹細胞の維持と巨核球の分化を制御する
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Geminlnは造血幹細胞の維持と巨核球の分化を制御する (2010)
  • Author(s): 中野星児、佐々木陽丞、本橋ほづみ、中山啓子
  • Organizer: 第33回分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] 第33回分子生物学会年会・第83回日本生化学会大会合同大会 (2010)
  • Author(s): 舟山亮, 細金正樹, 西田有一郎, 中山啓子
  • Organizer: がん遺伝子RASによる広範囲染色体領域の遺伝子サイレンシング機構の解析
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] 第33回分子生物学会年会・第83回日本生化学会大会合同大会 (2010)
  • Author(s): 細金正樹, 舟山亮, 西田有一郎, 中山啓子
  • Organizer: Ras-mediated gene silencingによるFas遺伝子領域のエピジェネティック制御
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] がん遺伝子RASによる広範囲染色体領域の遺伝子サイレンシング機構の解析 (2010)
  • Author(s): 舟山亮、細金正樹、西田有一郎、中山啓子
  • Organizer: 第33回分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Ras-mediated gene silencing によるFas遺伝.f領域のエピジェネティック制御 (2010)
  • Author(s): 細金正樹、舟山亮、西田有一郎、中山啓子
  • Organizer: 第33回分子生物学会年会第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-08
• [Presentation] Geminin negatively regulates thromhopoiesis (2010)
  • Author(s): Keiko Nakayama
  • Organizer: MEXT Priority Research Project "Cell Proliferation Control" International Symposium Cell Cycle and Cell Differentiation From A to Z
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-04
• [Presentation] がん遺伝子Rasは複数の遺伝子を含む広範囲な染色体領域を抑制する (2010)
  • Author(s): 細金正樹、舟山亮、中山啓子
  • Organizer: 日本分子生物学会第10回春季シンボジウム
  • Place of Presentation: 松島
  • Year and Date: 2010-06-07
• [Presentation] Ras-mediated regional silencing around Fas gene locus (2010)
  • Author(s): Masaki Hosogane, Ryo Funayama, Jafar Sharif, liaruhiko Koseki, Keiko Nakayam
  • Organizer: COLD SPRING HARBOR ASIA CONFERENCES, Epigenetics, Chromatin & 'Transcription
  • Place of Presentation: 蘇州、中国
  • Year and Date: 2010-05-18
• [Presentation] Ku80のユビキチン化を介したDNA二重鎖切断修復制御 (2009)
  • Author(s): 石田典子, 家村俊一郎, 安井明, 夏目徹, 中山啓子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] T-cell differentiation and proliferation in Geminin gene-deleted mouse (2009)
  • Author(s): 中野星児, 山田秀俊, 村井寛子, 佐竹正延, 中山啓子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] ユビキチンリガーゼSCFFbxw7はNotchタンパク質分解によりB細胞の分化を制御する (2009)
  • Author(s): 青山慧, 石川善則, 小野山一郎, 中山敬一, 中山啓子
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] 核内IKKβを介したNF-kB活性化による細胞死亢進 (2009)
  • Author(s): 土谷佳弘, 浅野知一郎, 中山啓子, 加藤友久, Michael Karin, 鎌田英明
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Chromobox homologue 3 is a essential modulator of endodermal and mesodermal differentiation in F9 cells (2009)
  • Author(s): 池田信人, 森川久未, 中野星児, 久留一郎, 白吉安昭
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Differential tissue specificity of ubiquitin ligase SCFFbxw7 (2009)
  • Author(s): 中山啓子
  • Organizer: 東北大学グローバルCOE Network Medicine創生拠点国際シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-12-07
• [Presentation] Defect of T-cell differentiation and proliferation in Geminin genedeleted mouse (2009)
  • Author(s): 中野星児
  • Organizer: 東北大学グローバルCOE Network Medicine創生拠点国際シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-12-07
• [Presentation] CSI Singapore, NUS-Tohoku University GCOE Joint Symposium (2009)
  • Author(s): 中山啓子
  • Organizer: Cell cycle control during differentiation : regulation by two F-box protein, Fbw7
  • Place of Presentation: Singapore
  • Year and Date: 2009-09-09
• [Presentation] Cell cycle control during differentiation : regulation by two F-box protein, Fbw7 (2009)
  • Author(s): 中山啓子
  • Organizer: CSI Singapore, NUS-Tohoku University GCOE Joint Symposium
  • Place of Presentation: シンガポール
  • Year and Date: 2009-09-09
• [Presentation] Differential specificity of substrate accumulation in ubiquitin ligase SCFFBXW7 deficient cells (2009)
  • Author(s): 中山啓子
  • Organizer: nstitite of Molecular and Cell Biology(IMCB)Cell Cycle Regulation and Tumorigenesis Symposium
  • Place of Presentation: シンガポール
  • Year and Date: 2009-09-07
• [Presentation] 第6回東北大学バイオサイエンスシンポジウム (2009)
  • Author(s): 山田秀俊, 中山啓子
  • Organizer: Gemininはmouse Embryonic Stem CellにおけるDNA複製と遺伝子発現を制御する
  • Place of Presentation: 仙台
  • Year and Date: 2009-06-16
• [Presentation] Gemininはmouse Embryonic Stem CellにおけるDNA複製と遺伝子発現を制御する (2009)
  • Author(s): 山田秀俊
  • Organizer: 第6回東北大学バイオサイエンスシンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2009-06-16
• [Presentation] 東北大学Network Medicine創生拠点冬の合宿 (2009)
  • Author(s): 中山啓子
  • Organizer: タンパク質の翻訳後修飾制御機構とその破綻による疾患発症メカニズムの解明
  • Place of Presentation: 仙台
  • Year and Date: 2009-02-14
• [Presentation] 東北大学Network Medicine創生拠点冬の合宿 (2009)
  • Author(s): 山田秀俊, 中山啓子
  • Organizer: GemininはMouse Embryonic Stem CellにおけるDNA複製と遺伝子発現を制御している
  • Place of Presentation: 仙台
  • Year and Date: 2009-02-14
• [Presentation] 新規RING-Fingerタンパク質はNAPIL1のユビキチン化を介して細胞増殖を抑制する (2008)
  • Author(s): 石田典子, et.al.
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] ユビキチンリガーゼSCF^<Fbxw7>はBリンパ球の分化.生存の抑制因子である (2008)
  • Author(s): 青山慧
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] ユビキチンリガーゼSCF^<Fbxw7>は表皮角化細胞において増殖と分化を抑制する (2008)
  • Author(s): 石川善則, et.al.
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] ノックインマウスを用いたp27とp57の機能的類似性と特異性の検討 (2008)
  • Author(s): 洲崎悦生, et.al.
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
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