Regulation of KIF3 motor by dephosphorylation

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Miyagi Cancer Center Research Institute
• Principal Investigator: SHIMA Hiroshi 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 部長 (10196462)
• Co-Investigator(Kenkyū-buntansha): YAMASITA Youzi 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 特任研究員 (30420045) ; WATANABE Tosio 奈良女子大学, 自然科学系, 教授 (60201208) ; SUGAMURA Kazuo 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 特任部長 (20117360)
• Project Period (FY): 2010 – 2012
• Keywords: 分子腫瘍学

Research Abstract

We identified the protein-phosphatase DUSP26 as a novel regulator of the KIF3 motor. Dusp26 is recruited to the KIF3 motor mainly by interaction with Kif3a, and thereby dephosphorylates Kap3. Enzyme activity of the Dusp26 was shown to promote distribution of beta-catenin/N-cadherinto cell-cell junction sites, resulting in increased cell-cell adhesiveness. We also showed that DUSP26 mRNA expression was downregulated in human glioblastoma samples, and a CpG island upstream of the DUSP26 transcrptional start site was heavily methylated in glioma cell lines. These results suggest previously unidentified functions of DUSP26 in intracellular transport and cell-cell adhesion.Downregulation of DUSP26 may contribute to malignant phenotypes of glioma. We showed that DUSP13B inactivated MAPK activation in the order of selectivity, JNK=p38> ERK in cells. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1 dependent gene expression. DUSP13B is the first identified testis specific phosphatase that inhibits stress-activated MAPKs.

Research Products

• [Journal Article] IDH1/2 gene status defines the prognosis and molecular profiles in patients with grade III gliomas. (2012)
  • Author(s): Shibahara I, Sonoda Y, Kanamori M, Saito R, Yamashita Y, Kumabe T, Watanabe M, Suzuki H, Kato S, Ishioka C, Tominaga T.
  • Journal Title: Int J Clin Oncol Volume: 17(6) Pages: 551-61
• [Journal Article] Novel function of MKP-5/DUSP10, a phosphatase for stress-activated kinases, on ERK dependent gene expression,and up-regulation of its gene expression in colon carcinomas (2012)
  • Author(s): Nomura M, Shiiba K-I, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, KatakuraR, Yamashita Y, Sato M, Tanuma N, Shima H
  • Journal Title: Oncol Rep. Volume: 28(3) Pages: 931-6
• [Journal Article] The clathrin assembly protein PICALMis required for erythroid maturationand transferrin internalization in mice (2012)
  • Author(s): Suzuki M, Tanaka H, Tanimura A, Tanabe K, Oe N, Rai S, Kon S, Fukumoto M,Takei K, Abe T, Matsumura I, Kanakura Y, Watanabe T.
  • Journal Title: PLoS One. Volume: 7(2) Pages: e31854
• [Journal Article] Sialidase NEU4 Hydrolyzes PolysialicAcids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons J.Biol.Chem. (2012)
  • Author(s): Takahashi K, Mitoma J, Hosono M, Shiozaki K, Sato C, Yamaguchi K, Kitajima K, Higashi H, Nitta K, Shima H, and Miyagi T
  • Journal Title: J.Biol.Chem. Volume: 287(18) Pages: 14816-26
• [Journal Article] DUSP13B/TMDPinhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression (2011)
  • Author(s): Katagiri C, Masuda K, Nomura M, Tanoue K, Fujita S, Yamashita Y, Katakura R, Shiiba K, Nomura E, Sato M, Tanuma N, Shima H
  • Journal Title: Molecular and Cellular Biochemistry Volume: 352(1-2) Pages: 155-162
• [Journal Article] MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm (2010)
  • Author(s): Masuda K, Katagiri C, Nomura M, SatoM, Kakumoto K, Akagi T, KikuchiK, Tanuma N, Shima H
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 393 Pages: 201-206
• [Journal Article] CDC25A mRNA levels significantly c orrelate with Ki-67 expression in human glioma samples (2010)
  • Author(s): Yamashita Y, Kasugai I, Sato M, Tanuma N, Sato I, Nomura M, Yamashita K,Sonoda Y, Kumabe T, Tominaga T, Katakura R, Shima H
  • Journal Title: Journal of Neuro-Oncology Volume: 100(1) Pages: 43-49
• [Journal Article] The phosphatase interactor NIPP1 regulates the occupancy of the histone methyltransferase EZH2 at Polycomb targets. (2010)
  • Author(s): Van Dessel N, Beke L, Gornemann J, Minnebo N, Beullens M, Tanuma N, Shima H, Van Eynde A, Bollen M.
  • Journal Title: Nucleic Acids Res. Volume: 38(21) Pages: 7500-7512
• [Presentation] Embryonic Lethality Caused in Mice LPP6c gene (2013)
  • Author(s): Ogoh H, Kishimoto A, Suzuki M, Hara K, Tanga N, Tanuma N, Watanabe T andShima H
  • Organizer: 10th International Conference on Protein Phosphatase
  • Place of Presentation: Tokyo
  • Year and Date: 20130207-09
• [Presentation] ピルビン酸キナーゼM(PKM)の発現アイソフォーム固定したマウスの作出 (2012)
  • Author(s): 田沼延公、岸本綾子、松本祥子、野村美有樹、近藤玄、国下侑里、片倉隆一、佐藤雅美、渡邊利雄、島礼
  • Organizer: 第85回日本生化学会
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] ピルビン酸キナーゼM2はダイオキシン受容体の活性化補助因子である (2012)
  • Author(s): 松田俊、足立淳、井原賢、田沼延公、島礼、井倉正枝、井倉毅、松田知成
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] ワールブルグ効果に関するin vivo解析のためのマウスモデル開発 (2012)
  • Author(s): 松本祥子、岸本綾子、国下侑里、近藤玄、野村美有樹、渡邊利雄、島礼、田沼延公
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] ES細胞におけるピルビン酸キナーゼM(PKM)アイソフォームの機能解析‐ノックイン細胞を用いて (2012)
  • Author(s): 田沼延公、岸本綾子、国下侑里、松本祥子、近藤玄、坂本良美、野村美有樹、渡邊利雄、島礼
  • Place of Presentation: 福岡
  • Year and Date: 20121211-14
• [Presentation] 悪性グリオーマ検体およびグリオーマ樹立株におけるPTPzetaの解析 (2012)
  • Author(s): 山下洋二、春日井勲、田沼延公、柴原一陽、園田順彦、金森政之、齋藤竜太、隅部俊宏、冨永悌二、島礼、片倉隆一
  • Organizer: 脳神経外科学会
  • Place of Presentation: 大阪
  • Year and Date: 20121017-19
• [Presentation] PKMスイッチ不可能なマウスモデル (2012)
  • Author(s): 田沼延公、渡邊利雄、野村美有樹、佐藤郁郎、椎葉健一、山下洋二、佐藤雅美、島礼
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] PP6触媒サブユニット遺伝子は、胚の初期発生時期に必須である (2012)
  • Author(s): 渡邊利雄、田沼延公、島礼
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20120919-21
• [Presentation] Switch of pyruvate kinase M (PKM) isoforms in human breast cancers (2011)
  • Author(s): 野村美有樹、田沼延公、角川陽一郎、島礼
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20111003-05
• [Presentation] Analysis of Protein Phosphatases in Human Glioma Samples (2011)
  • Author(s): Shima H
  • Organizer: 9th International Conference on Protein Phosphatase & Ist International Symposium on Carcinogenic Spiral
  • Place of Presentation: Tokyo
  • Year and Date: 20110201-03
• [Presentation] Phospho-Regulation of Splicesomal Protein, Sap155/Sf3b1 (2011)
  • Author(s): Tanuma N, Nomura M, Sato M, Yamashita Y, Shiiba K, Katakura K, and ShimaH
  • Organizer: 9th International Conference on Protein Phosphatase & Ist International Symposium on Carcinogenic Spiral
  • Place of Presentation: Tokyo
  • Year and Date: 20110201-03
• [Presentation] Embryonic Lethality Caused in Mice Lacking the phosphatase domain of thePP6c gene (2011)
  • Author(s): Kishimoto A, Tanuma N, Suzuki M, Sasaki, N Abe T, Kiyonari H, Aizawa S-i,Watanabe T, Shima H
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 20110011-16
• [Presentation] Protein Phosphatases in human Glioma Samples (2011)
  • Author(s): Shima H
  • Organizer: The first Japan-Taiwan Bilateral Conference on Protein Phosphatases
  • Place of Presentation: Okazaki
  • Year and Date: 2011-12-02
• [Presentation] Conversion of pyruvate kinase M (PKM) isozymes in human cancers - an analysis using isoform-specific antibodies (2010)
  • Author(s): 野村美有樹、田沼延公、佐々木希、島礼
  • Organizer: BMB 2010 第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Drift of pyruvate kinase M (PKM) alternative splicing associating with Warburg effect in human cancers (2010)
  • Author(s): 田沼延公、野村美有樹、大内司、佐藤雅美、片倉隆一、島礼
  • Organizer: BMB 2010 第33回日本分子生物学会年会、第83回日本生化学学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] Generation of isoform-specific antibodies against pyruvate kinase (PKM) (2010)
  • Author(s): 野村美有樹、田沼延公、山下洋二、椎葉健一、角川陽一郎、佐藤郁郎、島礼
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20100922-24
• [Presentation] Aberrant pre-mRNA splicing of pyrubate kinase M (PKM) in human cancer (2010)
  • Author(s): 田沼延公、野村美有樹、山下洋二、椎葉健一、角川陽一郎、佐藤郁郎、島礼
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 横浜
  • Year and Date: 20100922-24
• [Remarks]
  • URL: http://www.miyagi-pho.jp/mcc/kenkyu/yakubutsu.html