The Dlg signal transduction pathway

• Project/Area Number: 19390082
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: AKIYAMA Tetsu The University of Tokyo, 分子細胞生物学研究所, 教授 (70150745)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: Dlg / Runx / Wnt シグナル / sFRP2 / シグナル伝達 / 細胞膜裏打ち蛋白質 / beta-catenin / sFRP / 癌抑制遺伝子

Research Abstract

Dlg-Runx-sFRP2-Wntシグナル伝達経路の実体と生理的意義を明らかにすることを目的として研究を行い、以下の成果を得た。1)RunxがA-MybおよびRhoA特異的guanine nucleotide exchange factor Net1と複合体を形成することを見出した。3)Dlg-/-細胞ではProBからPreBへの分化に異常があることが確認された。4)Dlg-/-マウスでは、心室中核欠損、口蓋裂、腎泌尿器系の発生異常を起こすことを見出した。5)ヒト乳癌培養細胞株35種類についてDlgの変異が存在しないことを明らかにした。

Research Products

• [Journal Article] Gene set-based module discovery in the breast cancer transcriptome (2009)
  • Author(s): Niida A., Smith A. D., Imoto S., Aburatani H.,Zhang M. Q. and Akiyama T.
  • Journal Title: BMC Bioinformatics 10 Pages: 71-71
• [Journal Article] Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration (2009)
  • Author(s): Sagara M. , Kawasaki Y. , Iemura S. I., Natsume T., Takai Y., Akiyama T.
  • Journal Title: Oncogene 28 Pages: 1357-1365
• [Journal Article] Asef2 and Neurabin2 cooperatively regulate actin cytoskeletal organization and are involved in HGF-induced cell migration. (2009)
  • Author(s): Sagara M.
  • Journal Title: Oncogene 14 Pages: 14-14
• [Journal Article] Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer (2008)
  • Author(s): Togo N., Ohwada S., Sakurai S., Toya H., Sakamoto I., Yamada T., Nakano T., Muroya K., Takeyoshi I., Nakajima T., Sekiya T., Yamazumi Y., Nakamura T., Akiyama T.
  • Journal Title: World J. Gastroenterol 14 Pages: 4880-4888
• [Journal Article] Integrative bioinformatics analysis of transcriptional regulatory programs in breast cancer cells (2008)
  • Author(s): Niida A., Smith A. D., Imoto S., Tsutsumi S., Aburatani H., Zhang M. Q., Akiyama T.
  • Journal Title: BMC Bioinformatics 9 Pages: 404-404
• [Journal Article] Truncation mutations abolish chromatin-associated activities of adenomatous polyposis coli (2008)
  • Author(s): Kouzmenko A. P., Takeyama K., Kawasaki Y., Akiyama T., Kato S.
  • Journal Title: Oncogene 27 Pages: 4888-4899
• [Journal Article] Ligand-dependent interaction between estrogen receptor alpha and adenomatous polyposis coli (2008)
  • Author(s): Kouzmenko, A. P., Takeyama, K. I., Kawasaki,Y., Akiyama, T., Kato, S.
  • Journal Title: Genes Cells 13 Pages: 723-730
• [Journal Article] Phosphorylation and activation of a Rac1/Cdc42 guanine nucleotide exchange factor Asef in A431 cells stimulated by epidermal growth factor (2008)
  • Author(s): Itoh, R. E., Kiyokawa, E., Aoki, K., Nishioka, T., Akiyama, T., Matsuda, M.
  • Journal Title: J Cell Sci 121 Pages: 2635-2642
• [Journal Article] A human homolog of Notum, over-expressed in hepatocellular carcinoma, is transcriptionally regulated by β-catenin/TCF (2008)
  • Author(s): Torisu, Y., Watanabe, A., Nonaka, A., Midorikawa, Y., Makuuchi, M., Shimamura, T., Sugimura, H., Niida, A., Akiyama, T., Iwanari, H., Kodama, T., Zeniya, M., Aburatani, H.
  • Journal Title: Cancer Sci 99 Pages: 1139-1146
• [Journal Article] PX-RICS mediates ER-to-Golgi transport of the N-cadherin/β-catenin complex (2008)
  • Author(s): Nakamura T., Hayashi T., Yukiko Nasu-Nishimura Y., Sakaue F., Okabe T., Ohwada S., Matsuura K., Akiyama T.
  • Journal Title: Genes Dev 22 Pages: 1244-1256
• [Journal Article] Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin (2008)
  • Author(s): Haraguchi K., Ohsugi M., Abe Y., Semba K., Akiyama T., Yamamoto T.
  • Journal Title: Oncogene 27 Pages: 274-284
• [Journal Article] Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin (2008)
  • Author(s): Haraguchi K.
  • Journal Title: Oncogene 27 Pages: 274-284
• [Journal Article] PX-RICS mediates ER-to-Golgi transport of the N-cadherin/β-catenin complex. (2008)
  • Author(s): Nakamura T.
  • Journal Title: Genes Dev. 22 Pages: 1244-1256
• [Journal Article] A human homolog of Notum, over-expressed in hepatocellular carcinoma,is transcriptionally regulated by β-catenin/TCF. (2008)
  • Author(s): Torisu, Y.
  • Journal Title: Cancer Sci. 99 Pages: 1139-1146
• [Journal Article] Phosphorylatioh and activation of a Rac1/Cdc42 guanine nucleotide exchange factor Asef in A431 cells stimulated by epidermal growth factor. (2008)
  • Author(s): Itoh, R.
  • Journal Title: J Cell Sci. 121 Pages: 2635-2642
• [Journal Article] Ligand-dependent interaction between estrogen receptor alpha and adenomatouspolyposis coli. (2008)
  • Author(s): Kouzmenko, A. P.
  • Journal Title: Genes Cells 13 Pages: 723-730
• [Journal Article] Truncation mutations abolish chromatin-associated activities of adenomatous polyposis coli. (2008)
  • Author(s): Kouzmenko, A. P.
  • Journal Title: Oncogene 27 Pages: 4888-4899
• [Journal Article] Integrative bioinformatics analysis of transcriptional regulatory programs in breast cancer ceUs. (2008)
  • Author(s): Niida A.
  • Journal Title: BMC Bioinformatics 9 Pages: 404-404
• [Journal Article] Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer. (2008)
  • Author(s): Togo N
  • Journal Title: World J. Gastroenterol. 14 Pages: 4880-4888
• [Journal Article] Gene set-based module discovery in the breast cancer transcriptome (2008)
  • Author(s): Niida A.
  • Journal Title: BMC Bioinfbmatics 10 Pages: 71-71
• [Journal Article] A human homolog of Notum, over-expressed in hepatocellular carcinoma, is transcriptionally regulated by b-catenin/TCF (2008)
  • Author(s): Toya H.
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Journal Article] PX-RICS mediatesER-to-Golgi transport of the N-cadherin/b-catenin complex (2008)
  • Author(s): Nakamura T.
  • Journal Title: Genes Dev (in press)
  • Peer Reviewed
• [Journal Article] α-catenin is essential in intestinal adenoma formation (2007)
  • Author(s): Shibata, H., Takano, H., Ito, M., Shioya, H., Hirota, M., Matsumoto, H., Kakudo, Y., Ishioka, C., Akiyama, T., Kanegae, Y., Saito, I., Noda T.
  • Journal Title: Proc. Natl. Acad. Sci. USA. 104 Pages: 18199-18204
• [Journal Article] Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis (2007)
  • Author(s): Hasegawa, Y., Satoh, K., Iizuka-Kogo, A., Shimomura, A., Nomura, R., Akiyama, T., Senda, T.
  • Journal Title: Biochem. Biophys. Res. Commun 362 Pages: 988-994
• [Journal Article] Requirement of the tumor suppressor APC for the clustering of PSD-95 and AMPA receptors in hippocampal neurons (2007)
  • Author(s): Shimomura A., Ohkuma M., Iizuka-Kogo A., Kohu K., Nomura R., Miyachi E., Akiyama T., Senda T.
  • Journal Title: Eur. J. Neurosci 26
• [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast cancers (2007)
  • Author(s): Ito E., Honma R., Yanagisawa Y., Imai JI., Azuma S., Oyama T., Ohwada S., Akiyama T., Nomura N., Inoue JI., Watanabe S, Semba K.
  • Journal Title: FEBS Letters 581 Pages: 3909-3914
• [Journal Article] Identification and Characterization of Asef2, a guanine-nucleotide exchange factor specific for Rac1 and Cdc42 (2007)
  • Author(s): Kawasaki Y., Sagara M., Shibata S., Shirouzu M., Yokoyama S., Akiyama T.
  • Journal Title: Oncogene 26 Pages: 7620-7627
• [Journal Article] Helicobacter pylori CagA interacts with E-cadherin and deregulates the β-catenin signal that promotes intestinal transdifferentiation in gastric epithelial cells (2007)
  • Author(s): Murata-Kamiya, N., Kurashima, Y., Teishikata, Y., Yamahashi, Y., Saito, Y., Higashi, H., Aburatani, H., Akiyama, T., Peek Jr., R. M., Azuma, T., Hatakeyama, M.
  • Journal Title: Oncogene 26 Pages: 4617-4626
• [Journal Article] PX-RICS, a novel splicing variant of RICS, is a main isoform expressed during neural development (2007)
  • Author(s): Hayashi T., Okabe T., Nasu-Nishimura Y., Sakaue F., Ohwada S., Matsuura K., Akiyama T., Nakamura T.
  • Journal Title: Genes Cells 12 Pages: 929-939
• [Journal Article] PH-domain-mediated membrane targeting of Asef (2007)
  • Author(s): Muroya, K., Kawasaki, Y., Hayashi, T., Ohwada, S., Akiyama T.
  • Journal Title: Biochem. Biophys. Res. Commun 355 Pages: 85-88
• [Journal Article] Up-regulation of a BCL9-related beta-catenin-binding protein, B9L, in different stages of sporadic colorectal adenoma (2007)
  • Author(s): Sakamoto I., Ohwada S., Toya H., Togo N., Kashiwabara K., Oyama T., Nakajima T., Ito H., Adachi S., Jigami T., Akiyama T.
  • Journal Title: Cancer Sci 98 Pages: 83-87
• [Journal Article] Abnormal development of urogenital organs in Dlgh1-deficient mice (2007)
  • Author(s): Iizuka-Kogo A., Ishidao T., Akiyama T., Senda T.
  • Journal Title: Development(equal corresponding authors) 134 Pages: 1799-1807
• [Journal Article] Immunohistochemical expression of the beta-catenin-interacting protein B9L is associated with histological high nuclear grade and immunohistochemical ErbB2/HER-2 expression in breast cancers (2007)
  • Author(s): Toya H., Oyama T., Ohwada S., Togo N., Sakamoto I., Horiguchi J., Koibuchi Y., Adachi S., Jigami T., Nakajima T., Akiyama T.
  • Journal Title: Cancer Sci 98 Pages: 484-490
• [Journal Article] Crystal structure of the rac activator, asef, reveals its autoinhibitory mechanism (2007)
  • Author(s): Murayama K., Shirouzu M., Kawasaki Y., Kato-Murayama M., Hanawa-Suetsugu K., Sakamoto A., Katsura Y., Suenaga A., Toyama M., Terada T., Taiji M., Akiyama T., Yokoyama S.
  • Journal Title: J Biol Chem. 282 Pages: 4238-4242
• [Journal Article] Crystal structure of the racactivator, asef, reveals its autoinhibitory mechanism (2007)
  • Author(s): Murayama K.
  • Journal Title: J Biol Chem 282 Pages: 4238-4242
  • Peer Reviewed
• [Journal Article] Imlnunohistochemical expression of the beta-catenin-interacting protein B9L is associated with histological high nuclear grade and immunohistochemical ErbB2/HER-2 expression in breast cancers (2007)
  • Author(s): Toya H.
  • Journal Title: Cancer Sci 98 Pages: 484-490
  • Peer Reviewed
• [Journal Article] Abnormal development of urogenital organs in Dlgh1-deficient mice. (2007)
  • Author(s): Iizuka-Kogo A.
  • Journal Title: Development 134 Pages: 1799-1807
  • Peer Reviewed
• [Journal Article] Up-regulation of a BCL9-related beta-catenin-binding protein, B9L, in different stages of sporadic colorectal adenoma (2007)
  • Author(s): Sakamoto I.
  • Journal Title: Cancer Sci 98 Pages: 83-87
  • Peer Reviewed
• [Journal Article] PH-domain-mediated membrane targeting of Asef. Biochem. Biophys. Res (2007)
  • Author(s): Muroya, K.
  • Journal Title: Biophys. Res. Commun. 355 Pages: 85-88
  • Peer Reviewed
• [Journal Article] PX-RICS,a novel splicing variant of RICS, is a main isoform expressed during neural development (2007)
  • Author(s): Hayashi T.
  • Journal Title: Genes Cells 12 Pages: 929-939
  • Peer Reviewed
• [Journal Article] Crystal structure of the rac activator, asef, reveals its autoinhibitory mechanism (2007)
  • Author(s): Murata-Kamiya, N.
  • Journal Title: The Journal of biological chemistry 282 Pages: 4238-4242
  • Peer Reviewed
• [Journal Article] Kawasaki Y. Identification and Characterization of Asef2, a guanine-nucleotide exchange factor specfic for Racl and Cdc42 (2007)
  • Author(s): Kawasaki Y.
  • Journal Title: Oncogene 26 Pages: 7620-7627
  • Peer Reviewed
• [Journal Article] a-catenin is essential in intestinal adenoma formation (2007)
  • Author(s): Shibata H.
  • Journal Title: Proc. Natl. Acad. Sci. USA 104 Pages: 18199-18204
  • Peer Reviewed
• [Journal Article] Novel clusters of highly expressed genes accompany genomic amplification in breast (2007)
  • Author(s): Ito E.
  • Journal Title: FEBS Letters 581 Pages: 3909-3914
  • Peer Reviewed
• [Journal Article] Requirement of the tumor suppressor APC for the clustering of PSD-95 and AMPA receptors in hipPocampal neurons (2007)
  • Author(s): Shimomura A.
  • Journal Title: Eur. J. Neurosci 26
  • Peer Reviewed
• [Journal Article] Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenes (2007)
  • Author(s): Hasegaw Y.
  • Journal Title: Biochem. Biophys. Res. Commun 362 Pages: 988-994
  • Peer Reviewed