奈良先端科学技術大学院大学 動物細胞工学研究室(河野研)

Publications

原著論文

2017

  • Sato, H., Shiba, Y., Tuchiya, Y., Saito, M., Kohno, K. 4μ8C inhibits insulin secretion independent of IRE1α RNase activity. Cell Struct Funct. doi: 10.1247/csf.17002.(2017)  

2016

  • Kanda, S., Yanagitani, K., Yokota, Y., Esaki, Y., Kohno, K. Autonomous translational pausing is required for XBP1u mRNA recruitment to the ER via the SRP pathway. Proc. Natl. Acad. Sci. U.S.A. 113(40):E5886-E5895.(2016)  
  • Le, Q.G,, Ishiwata-Kimata, Y., Kohno, K. and Kimata, Y. Cadmium impairs protein folding in the endoplasmic reticulum and induces the unfolded protein response. FEMS Yeast Research pii: fow049. doi: 10.1093/femsyr/fow049 (2016)  
  • Tsuchiya Y, Saito M, Kohno K. Pathogenic Mechanism of Diabetes Development Due to Dysfunction of Unfolded Protein Response. Yakugaku Zasshi 136(6):817-25.(2016)  
  • Tsuru, A., Imai, Y., Saito, M.,and Kohno, K. Novel mechanism of enhancing IRE1α-XBP1 signalling via the PERK-ATF4 pathway. Sci. Rep DOI: 10.1038. (2016)  

2015

  • 小池雅昭,河野憲二 「タンパク質品質管理」 生体の科学 増大特集「細胞シグナル操作法」(医学書院) 66(5) 490-491(2015)  
  • Takaori, K., Nakamura, J., Yamamoto, S., Nakata, H., Sato, Y., Takase, M., Nameta, M., Yamamoto, T., Economides, A.N., Kohno, K., Sharma, K., Yanagita M. Severity and frequency of proximal tubule injury determines renal prognosis. J. Am. Soc. Nephrol.(2015) Dec 23. [Epub ahead of print] 
  • Hirai SI, Kurashima H, Nakamura D, Komatsu T, Yasuda Y, Habashita-Obata S, Ichikawa S, Katsuta O, Iwawaki T, Kohno K. 2-Phenyl-APB-144-Induced Retinal Pigment Epithelium Degeneration and Its Underlying Mechanisms. J Ocul Pharmacol Ther (2015) Aug 27. [Epub ahead of print] 
  • Mathuranyanon, R., Tsukamoto, T., Takeuchi, A., Ishiwata-Kimata, Y., Tuchiya, Y., Kohno, K., and Kimata, Y. Tight regulation of the unfolded protein sensor Ire1 by its intramolecularly antagonizing subdomain. J Cell Sci. ,128, 1762-1772 (2014) 

2014

  • 都留秋雄,河野憲二 「小胞体ストレスと炎症性腸疾患」 実験医学(羊土社) 32巻,14号 2221-2225 (2014)  
  • Yanagitani, K. and Kohno, K. Nascent chain-mediated localization of mRNA on the endoplasmic reticulum as an important step of unfolded protein response. Ed. by Koreaki Ito, in “Regulatory Nascent Polypeptides” Springer; DOI 10.1007/978-4-431-55052-5 DOI: pp. 291-310, (2014)  
  • Fujimoto, T., Matsui, T., Nitanda, Y., Matta, T., Sakumura, Y., Saito, M., Kohno, K., Nakahara, Y., and Bessho, Y. Hes7 3'UTR is required for somite segmentation function. Sci Rep ,Sep 24;4 :6462 (2014)
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  • Shinomura, M., Kishi, K., Tomita, A., Kawasumi, M., Kanezashi, H., Kuroda, Y., Tsunekawa, N., Ozawa, A., Aiyama, Y., Yoneda, A., Suzuki, H., Saito, M., Picard, JY., Kohno, K., Kurohmaru, M., Kanai-Azuma, M., and Kanai Y. A novel Amh-Treck transgenic mouse line allows toxin-dependent loss of supporting cells in gonads. Reproduction 148(6), H1-9 (2014)
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  • Miyagawa, K., Ishiwata-Kimata, Y., Kohno, K., and Kimata, Y. Ethanol stress impairs protein folding in the endoplasmic reticulum and activates Ire1 in Saccharomyces cerevisiae. Biosci Biotechnol Biochem. , 78, 1389-1391 (2014)
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  • Nitanda, Y., Matsui, T., Matta, T., Higami, A., Kohno, K., Nakahata, Y., and Bessho, Y. 3'-UTR-dependent regulation of mRNA turnover is critical for differential distribution patterns of cyclic gene mRNAs. FEBS J. , 281, 146-156 (2014)
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  • Kim, SK., Nasu, A., Komori, J., Shimizu, T., Matsumoto, Y., Minaki, Y., Kohno, K., Shimizu, K., Uemoto, S., Chiba, T., Marusawa, H. A model of liver carcinogenesis originating from hepatic progenitor cells with accumulation of genetic alterations. Int J Cancer. 134(5), 1067-1076 (2014)
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2013

  • Kadokura H., S aito, M., Tsuru, A., Hosoda, A., Iwawaki, T., Inaba, K., and Kohno, K. Identification of the redox partners of ERdj5/JPDI, a PDI family member, from an animal tissue. Biochem. Biophys. Res. Commun. 440(2), 245-250 (2013)
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  • Adolph, T.E., Tomczak, M.F., Niederreiter, L., Ko, H.J., Böck, J., Martinez-Naves, E., Glickman, J.N., Tschurtschenthaler, M., Hartwig, J., Hosomi, S., Flak, M.B., Cusick, J.L., Kohno, K., Iwawaki, T., Billmann-Born, S., Raine, T., Bharti, R., Lucius, R., Kweon, M.N., Marciniak, S.J., Choi, A., Hagen, S.J., Schreiber, S., Rosenstiel, P., Kaser, A., and Blumberg, R.S. Paneth cells as a site of origin for intestinal inflammation. Nature , 503, 272-276 (2013)
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  • Niederreiter, L., Fritz, T.M.J., Adolph, T.E., Krismer, A.M., Offner, F. A., Tschurtschenthaler, M., Flak, M. B., Hosomi, S., Tomczak, M. F., Kaneider, N. C., Sarcevic, E., Kempster, S. L., Raine, T., Esser, D., Rosenstiel, P., Kohno, K., Iwawaki, T., Tilg, H., Blumberg, R. S., and Kaser, A. ER stress transcription factor Xbp1 suppresses intestinal tumourigenesis and directs intestinal stem cells. J. Exp. Med. 210(10), 2041-2056 (2013)
  • | Abstract | | PDF |
  • Dimitrov, E.L., Kuo, J., Kohno, K., and Usdin, T.B. Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues. Proc. Natl. Acad. Sci. U.S.A. 110(32), 13156-13161 (2013)
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  • Matsuoka, K., Saito, M., Shibata, K., Sekine, M., Shitara, H., Taya, C., Zhang, X., Takahashi, T.A., Kohno, K., Kikkawa, Y., and Yonekawa, H. Generation of mouse models for type 1 diabetes by selective depletion of pancreatic beta cells using toxin receptor-mediated cell knockout. Biochem. Biophys. Res. Commun. ,436(3), 400-405 (2013)
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  • Ishiwata-Kimata, Y., Yamamoto, Y.H., Takizawa, K., Hiraoka, Y., Kohno, K., and Kimata Y. Actin filaments are required for efficient clustering of endoplasmic stress sensor Ire1. Cell Struct. Funct. ,38(2), 135-143 (2013)
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  • Nguyen, L.S.T., Kohno, K., and Kimata, Y. Zinc depletion activates the endoplasic reticulum-stress sensor Ire1 via pleiotropic mechanisms. Biosci. Biotechnol. Biochem. 77(6), 1337-1339 (2013)
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  • Josekutty, J., Iqbal, J., Iwawaki, T., Kohno, K., and Hussain, M. MTP inhibition induces ER stress and increases gene transcription via Ire1α/cJun to enhance plasma ALT/AST. J. Biol. Chem. Epub ahead of Print, Mar 26 (2013)
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  • Matsuoka, K., Shitara, H., Taya, C., Kohno, K., Kikkawa, Y., and Yonekawa, H. Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation. PLoS One. 8, April e60958 (2013)
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  • Ishiwata-Kimata, Y., Promlek, T., Kohno, K., and Kimata, Y. BiP-bound and non-clustered mode of Ire1 evokes a weak but sustained unfolded protein response. Genes Cells, 18(4), 288-301 (2013)
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  • Tsuru, A., Fujimoto, N., Takahashi, S., Saito, M., Nakamura, D., Iwano, M., Iwawaki, T., Kadokura, H., Ron, D., and Kohno, K. Negative feedback by IRE1β optimizes mucin production in goblet cells. Proc Natl Acad Sci USA, 110 (8), 2864-2869 (2013)
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    ・Recommended by Faculty of 1000prime
  • Huang, J., Li, X., Kohno, K., Hatano, M., Tokuhisa, T., Murray, P.J., Brocker, T., and Tsuji, M. Generation of tissue-specific H-2Kd transgenic mice for the study of Kd-restricted malaria epitope-specific CD8+ T-cell responses in vivo. J. Immunonol. Methods, 387 (1-2), 254-261 (2013)
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2012

  • Jinde, S., Zsiros, V., Jiang, Z., Nakano, K., Pickel, J., Kohno, K., Belforte, J.E., and Nakazawa, K. Hilar mossy cell degeneration causes transient dentate granule cell hyperexcitability and impaired pattern separation. Neuron, 76(6), 1189-1200 (2012)
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  • Sopha, P., Kadokura, H., Yamamoto, Y. H., Takeuchi, M., Saito, M., Tsuru, A., and Kohno, K. A novel mammalian ER-located J-protein, DNAJB14, can accelerate ERAD of misfolded membrane proteins. Cell Struct. Funct. 37, 177-187 (2012)
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  • Chng, S.S., Xue, M., Garner, R.A., Kadokura, H., Boyd, D., Beckwith, J., Kahne D. Disulfide rearrangement triggered by translocon assembly controls lipopolysaccharide export. Science 337, 1665-1668 (2012)
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  • Kamimura, R., Ishii, T., Sasaki, N., Kajiwara, M., Machimoto, T., Saito, M., Kohno, K., Suemori, H., Nakatsuji, N., Ikai, I., Yasuchika, K., and Uemoto, S. Comparative study of transplantation of hepatocytes at various differentiation stages into mice with lethal liver damage.
    Cell Transplantation, Apr 2 (ahead of print) (2012)
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2011

  • Kim, W., Matsui, T., Yamao, M., Ishibashi, M., Tamada, K., Takumi, T., Kohno, K., Oba, S., Ihii, S., Sakumura, Y., and Bessho, Y. The period of the somite segmentation clock is sensitive to Notch activity. Mol. Biol. Cell, 22, 3541-3549 (2011)
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  • Promlek, T., Ishiwata-Kimata, Y., Shido, M., Sakuramoto, M., Kohno, K. and Kimata, Y. Membrane aberrancy and unfolded proteins activate the endoplasmic reticulum-stress sensor Ire1 by different manners. Mol. Biol. Cell, 22, 3520-3532 (2011)
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    ・selected as a Highlighted Article
  • Kimata, Y., and Kohno, K. ER stress-sensing mechanisms in yeast and mammalian cells. Curr. Opin. Cell Biol.(2), 135-142, (2011)
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  • Sekine, M., Monkawa, T., Morizane, R., Matsuoka, K., Taya, C., Akita, Y., Joh, K., Itoh, H., Hayashi, M., Kikkawa, Y., Kohno, K., Suzuki, A., and Yonekawa, H. Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury. Transgenic Res.In press. doi: 10.1007/s11248-011-9504-z (2011)
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  • Shinya, S., Kadokura, H., Imagawa, Y., Inoue, M., Yanagitani, K., and Kohno, K. Reconstitution and characterization of the unconventional splicing of XBP1u mRNA in vitro. Nucleic Acids Research, 1-10 [Epub ahead of print] published online March 11, 2011, doi:10.1093/nar/gkr132 (2011)
    Abstract | PDF |
    ・selected as a Featured Article (top 5% of NAR).
  • Yanagitani, K., Kimata, Y., Kadokura, H., and Kohno, K. Translational Pausing Ensures Membrane Targeting and Cytoplasmic Splicing of XBP1u mRNA.Science 331, 586-589 (2011)
    Abstract | PDF | 朝日 科学新聞 日刊工業 産経,奈良,日経,日経産業 |
    ・ picked up by Science Express; published online 13 January 2011[DOI:10.1126/science.1197142]
    ・ picked up by Perspectives: D. Ron, and K. Ito. A translational pause to localize. Science 331, 543-544 (2011)
    ・ Faculty of 1000, evaluated as “Exceptional (10)”
    ・ Editor’s choice: S. M. Hurtley, Time for a pause. Sci. Signal. 4, ec41 (2011)
  • Nakamura, D., Tsuru, A., Ikegami, K., Imagawa, Y., Fujimoto, N., and Kohno, K. Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins. FEBS Lett. 585, 133-138 (2011)
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2010

  • Yamamoto, YH., Kimura, T., Momohara, S., Takeuchi, M., Kimata, Y., Kadokura, H., and Kohno, K. A novel ER J-protein DNAJB12 accelerates ER-associated degradation of membrane proteins including CFTR.Cell Struct. Funct. 35, 107-116 (2010)
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    ・selected as a 2010 CSF Award on Japan Society for Cell Biology
  • Omatsu, Y., Sugiyama, T., Kohara, H., Kohdoh, G., Fujii, N., Kohno, K., and Nagasawa, T. The essential functions of adipo-osteogenic progenitors as the hematopoietic stem and progenitor cell niche. Immunity 33, 387-399 (2010)
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  • Iwawaki, T., Akai, R., and Kohno, K. IRE1α disruption causes histological abnormality of exocrine tissues, increse of blood glucose level, and decrease of serum immunoglobulin level. PLoS ONE 5, e13052 (2010)
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  • Tsukano, H., Gotoh, T., Endo, M., Miyata, K., Tazume, H., Kadomatsu, T., Yano, M., Iwawaki, T., Kohno, K., Araki, K., Mizuta, H., and Oike, Y. The endoplasmic reticulum stress-CHOP pathway-mediated apoptosis in macrophages contributes to the instability of atherosclerotic plaques. Arteriosclerosis, Thrombosis, and Vascular Biology 30, 1925-1932 (2010)
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  • Abematsu, M., Tsujimura, K., Yamano, M., Saito, M., Kohno, K., Kohyama, J., Namihira, M., Komiya, S., and Nakashima, K. Neurons derived from transplanted neural stem cells restore disrupted neuronal circuitry in a mouse model of spinal cord injury. J. Clin. Inv. 120, 3255-3266 (2010)
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  • Ohtsu I., Wiriyathanawudhiwong N., Morigasaki S., Nakatani T., Kadokura H., and Takagi H. The L-cysteine/L-cystine shuttle system provides reducing equivalents to the periplasm in Escherichia coli. J. Biol. Chem. 285, 17479-17487 (2010)
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  • Thorel, F., Nepote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S., and Herrera, P.L. Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature 464, 1149-1154 (2010)
    → 新聞記事
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  • Kadokura H. and Beckwith J. Mechanisms of Oxidative Protein Folding in the Bacterial Cell Envelope. Antioxid. Redox. Signal. 13, 1231-1246 (2010)
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  • Ariyasu H, Iwakura H, Yamada G, Kanamoto N, Bando M, Kohno K, Sato T, Kojima M, Nakao K, Kangawa K, Akamizu T. A Postweaning Reduction in Circulating Ghrelin Temporarily Alters Growth Hormone (GH) Responsiveness to GH-Releasing Hormone in Male Mice But Does Not Affect Somatic Growth. Endocrinol. 151, 1743-1750 (2010)
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  • Kohno, K. Stress sensing mechanisms in the unfolded protein response: similarities and differences between yeast and mammals. J. Biochem. 147, 27-33 (2010)
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  • Hosoda, A., Tokuda, M., Akai, R., Kohno, K.,and Iwawaki, T. Positive contribution of ERdj5/JPDI to endoplasmic reticulum protein quality control in the salivary gland. Biochem. J. 425, 117-125 (2010)
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2009

  • Yoshiuchi, K., Kaneto, H., Matsuoka, T. A, Kasami, R., Kohno, K., Iwawaki, T., Nakatani, Y., Yamasaki, Y., Shimomura, I., and Matsuhisa, M. Pioglitazone reduces ER stress in the liver: Direct monitoring of in vivo ER stress using ER stress-activated indicator transgenic mice. Endocr. J. 56, 1103-1111 (2009)
  • Iwawaki, T., Akai, R., Yamanaka, S., and Kohno, K. Function of IRE1α in the placenta is essential for placental development and embryonic viability. Proc Natl Acad Sci USA 106, 16657-16662 (2009)
    • Editor’s choice: B. A. Purnell; Pregnancy can be stressful. Science 326, 206-207, 9 October (2009)
  • Kadokura H. and Beckwith J. Detecting folding intermediates of a protein as it passes through the bacterial translocation channel. Cell 138, 1164-1173 (2009)
  • Oikawa, D., Kimata Y., Kohno, K., and Iwawaki, T. Activation of mammalian IRE1α upon ER stress depends on dissociation of BiP rather than on direct interaction with unfolded proteins. Exp. Cell Res 315., 2496-2504 (2009)
  • Hayashi S, Shimoda T, Nakajima M, Tsukada Y, Sakumura Y, Dale JK, Maroto M, Kohno K, Matsui T, Bessho Y.Sprouty4, an FGF inhibitor, displays cyclic gene expression under the control of the Notch segmentation clock in the mouse PSM. PLoS ONE 4(5), e5603 (2009)
  • Yanagitani K., Imagawa Y., Iwawaki T., Hosoda A., Saito M., Kimata Y., and Kohno K. Cotranslational targeting of XBP1 protein to the membrane promotes cytoplasmic splicing of its own mRNA. Mol. Cell 34, 191-200 (2009)
    • Journal cover and its caption
    • Previews: D. Ron; Targeting of mRNAs to their sites of unconventional splicing in the unfolded protein response. Mol. Cell34, 133–134 (2009)
    • Editor’s choice: E. M. Adler; Dragged by a Newborn Peptide. Sci. Signal. 2 (68), ec145 (2009)
    → 新聞記事
  • Ogawa, T., Hidaka, M., Kohno, K., Masaki, H. Colicin E5 ribonuclease domain cleaves Saccharomyces cerevisiae tRNAs leading to impairment of the cell growth. J. Biochem. 145, 461-466 (2009)
  • Suzuki, H., Kanekura, K., Levine, T., Kohno, K., Olkkonen, V.M., Aiso, S., and Matsuoka M. ALS-linked P56S-VAPB, an aggregated loss-of-function mutant of VAPB, predisposes motor neurons to ER stress-induced death by inducing aggregation of co-expressed wild-type VAPB. J. Neurochem. 108, 973-985 (2009)

2008

  • Takada, T., Shitara, H., Matsuoka, K., Kojima, E., Kikkawa, Y., Karasuyama, H., Kohno, K., and Yonekawa, H. A novel hairless mouse model on an atopic dermatitis-prone genetic background generated by receptor-mediated transgenesis.Transgenic Res. 17, 1155-1162 (2008)
  • Takeuchi, M., Kimata, Y., and Kohno, K. Saccharomyces cerevisiae Rot1 is an essential molecular chaperone in the endoplasmic reticulum. Mol. Biol. Cell 19, 3514-3525 (2008)
  • Imagawa, Y., Hosoda, A., Sasaka, S., Tsuru, A., and Kohno, K. RNase domains determine the functional difference between IRE1α and IRE1β. FEBS Lett. 582, 656-660 (2008)

  • Yoshiuchi, K., Kaneto, H., Matsuoka, T. A., Kohno, K., Iwawaki, T., Nakatani, Y., Yamasaki, Y., Hori, M., Matsuhisa, M. Direct monitoring of in vivo ER stress during the development of insulin resistance with ER stress-activated indicator transgenic mice. Biochem. Biophys. Res. Commun. 366, 545-550 (2008)
     

2007

  • Ishii, T., Yasuchika, K., Machimoto, T., Kamo, N., Komori, J., Konishi, S., Suemori, H., Nakatsuji, N., Saito, M., Kohno, K., Uemoto, S., and Ikai, I. Transplantation of embryonic stem cell-derived endodermal cells into mice with life-threatening liver injury damage. Stem Cells 25(12), 2295-2303 (2007)
  • Machimoto, T., Yasuchika, K., Komori, J., Ishii, T., Kamo, N., Shimoda, M., Konishi, S., Saito, M., Kohno, K., Uemoto, S., and Ikai, I. Improvement of survival rate by fetal liver cell transplantation in a mice lethal liver failure model.Transplantation 84(10), 1233-1239 (2007)
  • Kohno, K. How transmembrane proteins sense endoplasmic reticulum stress. Antioxid. Redox Signal. 9, 2295-2303 (2007)
  • Schröder, M., and Kohno, K. Recent advances in understanding the unfolded protein response. Antioxid. Redox Signal. 9, 2241-2244 (2007)

  • Kimata, Y., Ishiwata-Kimata, Y., Ito, T., Hirata, A., Suzuki, T., Oikawa, D., Takeuchi, M., and Kohno, K. Two regulatory steps of ER-stress sensor Ire1 involving its cluster formation and interaction to unfolded proteins. J. Cell Biol. 179, 75-86 (2007)
    小胞体ストレスセンサーIre1が、ストレスに応じていかに活性化するかを明らかにした。第1段階では、小胞体分子シャペロンBiP(Ire1の抑制因子)の解離に伴い、Ire1はクラスター化する。第2段階では、構造異常蛋白質がIre1クラスターに直接結合し、Ire1の構造が活性化に適したものになる。この2段階の制御により、応答の正確性が保証されているのであろう。 → 新聞記事など

  • Kimura, Y., Saito, M., Kimata, Y., and Kohno, K. Transgenic mice expressing a fully nontoxic diphtheria toxin mutant, not CRM197 mutant, acquire immune tolerance against diphtheria toxin. J. Biochem. 142, 105-112 (2007)
  • Tatsumi, S., Ishii, K., Amizuka, N., Li, M., Kobayashi, T., Kohno, K., Ito, M., Takeshita, S., and Ikeda, K. Targeted ablation of osteocytes causes osteoporosis with defective mechanotranduction. Cell Mtabol. 5, 464-475 (2007)
  • Miyake, Y., Kaise, H., Isono, K., Koseki, H., Kohno, K., and Tanaka, M. Protective role of alveolar macrophages in non-inflammatory lung injury caused by selective ablation of alveolar epithelial type II cells. J. Immunol. 15, 5001-5009 (2007)

  • Oikawa, D., Kimata, Y. and Kohno, K. Self-association and BiP dissociation are not sufficient for activation of the endoplasmic reticulum-stress sensor Ire1. J. Cell Sci. 120, 1681-1688 (2007)
    真核細胞において、分泌系蛋白質の変性状態での小胞体への蓄積は、ストレス応答性蛋白質Ire1の活性化を促す。Ire1は通常時には単量体であり、ストレスに応じて多量体(もしくは二量体)化する。今回我々は、恒常的に多量体化しているIre1変異体も活性化についてはストレス誘導性であり、よって、多量体化は活性化の十分条件ではないことを示した。

2006

  • Furukawa, N., Saito, M., Hakoshima, T. and Kohno, K. A diphtheria toxin receptor deficient in epidermal growth factor-like biological activity. J. Biochem. 140, 831-841 (2006)
    細胞の生理機能解析を行うために、私たちは以前に毒素受容体を用いた細胞ノックアウト法を開発した。この方法では、ヒトのヘパリン結合性EGF様増殖因子 (HB-EGF)を毒素受容体として標的細胞に用いていた。今回私たちは、EGF様活性の副作用なしに細胞をノックアウトするために、HB-EGFのアミノ酸を置換することで、EGF様活性を失いつつ毒素受容体機能を保持した新規の毒素受容体を作製した。
  • Takeuchi, M., Kimata, Y., and Kohno, K. Causal links between protein folding in the ER and events along the secretory pathway. Autophagy 2, 323-324 (2006)
    我々は、小胞体内在性Hsp70の補助因子候補として小胞体膜蛋白質Rot1を同定した。Rot1は、細胞壁合成酵素などの折り畳みに関与していると考えられる。

  • Yamada, S., Yamaguchi, T., Hosoda, A., Iwawaki, T., and Kohno, K. Regulation of human STARD4 gene expression under endoplasmic reticulum stress. Biochem. Biophys. Res. Commun. 343, 1079-85(2006)
    小胞体ストレスに応答する遺伝子として、脂質代謝や脂質の運搬に関与するSTARD4を単離した。STARD4は小胞体ストレスに呼応して早期に転写レベルでの誘導がかかりかつ急速に誘導が終結する興味深い転写発現パターンを示した。プロモーター部を解析したところ、この転写には、転写因子ATF6と ERSE配列が関与していることが明らかとなった。

  • Takeuchi, M., Kimata, Y., Hirata, A., Oka, M., and Kohno, K. Saccharomyces cerevisiae Rot1p Is an ER-Localized Membrane Protein That May Function with BiP/Kar2p in Protein Folding. J. Biochem. 139, 597-605 (2006)
    小胞体内在性Hsp70(BiP/Kar2p)の新規補助因子を探索、出芽酵母必須遺伝子ROT1を得た。ROT1は複数の小胞体シャペロン遺伝子と遺伝学的相互作用を示し、小胞体に局在するI型膜蛋白質をコードする。Rot1pはKar2pと複合体を形成し、kar2-1 rot1-2二重変異によりモデル蛋白質の成熟に異常を生じた。Rot1pはKar2pと協力して蛋白質折り畳みに寄与すると推測している。
  • Kimata, Y., Ishiwata-Kimata, Y., Yamada, S., and Kohno, K. Yeast unfolded protein response pathway regulates expression of genes for anti-oxidative stress and for cell surface proteins. Genes Cells 11, 59-69 (2006)
    真核生物では小胞体ストレスに応じて遺伝子発現が変化することが知られており、Unfolded Protein Response (UPR)と呼ばれている。DNAマイクロアレイで調べた結果、出芽酵母Ire1-HAC1経路によるUPRの標的遺伝子として、新規なものを数多く発見した。例えば、分泌蛋白質や細胞表層蛋白質をコードする遺伝子の発現が抑えられた。これは、小胞体ストレス時に新生蛋白質が小胞体に流入するのを減らし、小胞体の負荷を軽くする意義があると考えられる。

2005

  • Chen, H., Kohno, K., and Gong, Q. Conditional ablation of mature olfactory sensory neurons mediated by diphtheria toxin receptor. J. Neurocytol. 34, 37-47 (2005)
    TRECK法を用いて成熟嗅覚神経細胞を特異的に除去できるトランスジェニックマウスを作製した。ジフテリア毒素を投与すると選択的に嗅覚神経細胞障害を生じ、GAP43陽性の未成熟な嗅覚神経前駆細胞の増殖昂進が観察された。このマウスは嗅覚神経細胞の生成やその制御の研究に有用である。
  • Wharram, B.L., Goyal, M., Wiggins, J.E., Sanden, S.K., Hussain, S., Filipiak, W.E., Saunders, T.L., Dysko, R.C., Kohno, K., Holzman, L.B. and Wiggins, R.C. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene. J. Am. Soc. Nephrol. 16, 2941-2952 (2005)
    TRECK法により、腎臓有足細胞特異的にジフテリア毒素受容体を発現するトランスジェニックラットを作製し、有足細胞の破壊と腎糸球体硬化症との関係について調べた。このトランスジェニックラットに毒素を投与すると毒素投与量に依存した有足細胞の破壊が観察され、有足細胞の破壊の程度と糸球体硬化症の程度が良く相関していることが明らかとなった。この結果は糸球体硬化症による腎機能の低下は有足細胞の機能障害によるものであることを強く支持している。
  • Oikawa, D., Kimata, Y., Takeuchi, M., and Kohno, K. An essential dimer-forming subregion of the endoplasmic reticulum stress sensor Ire1. Biochem. J. 391, 135-42 (2005)
    小胞体ストレスセンサーである酵母Ire1の小胞体内腔領域の機能を主に組換えタンパク質を用いて解析した。内腔領域は5つの領域に分けられるが、領域 2/4の部分はプロテアーゼ耐性及びホモダイマー形成能をもつこと、特に変異型Ire1を用いた解析から領域4がIre1のホモダイマー形成に強くかかわっていることが示唆された。
  • Nobukuni, Y., Kohno, K., and Miyagawa, K. Gene trap mutagenesis-based forward genetic approach reveals that the tumor suppressor OVCA1 is a component of the biosynthetic pathway of diphthamide on elongation factor-2. J. Biol. Chem. 280, 10572-10577 (2005)
    CHO細胞を用いてレトロウィルスを利用した遺伝子トラップライブラリーを構築し、ジフテリア毒素に耐性の変異株を単離したところ、ガン抑制遺伝子 OVCA1の変異株が取得された。この変異株は毒素の標的分子であるEF-2が毒素に耐性を示すもので、さらなる詳細な解析により、OVCA1が、EF- 2の翻訳後修飾、すなわちジフタマイド形成に関わる新規の生理機能をもつことが明らかになった。

2004

  • Kimata, Y., Oikawa, D., Shimizu, Y., Ishiwata-Kimata, Y., and Kohno, K. A role for BiP as an adjustor for the endoplasmic reticulum stress-sensing protein Ire1. J. Cell Biol. 167, 445-456 (2004)
    小胞体ストレスセンサーであるIre1のストレス感知機構を、一連の変異型Ire1を作製し酵母で発現させることにより解析した。この結果は、今までの「小胞体シャペロンBiPの結合解離によるIre1活性化の制御」仮説を覆すものであった。すなわち、Ire1がより直接的に小胞体ストレス感知を行っており、BiPの役割はIre1の活性化を小胞体ストレスのみに応答するよう制御すること、であることを示した。
  • Iwawaki, T., Akai, R., Kohno, K., and Miura, M. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat. Med. 10, 98-102 (2004)
    動物細胞で小胞体ストレス応答を鋭敏に検出し可視化できるシステムを構築し、そのシステムを組み込んだERAIトランスジェニックマウスを作製した。このマウスでは、小胞体ストレスを 起こしている組織や細胞が緑色蛍光を発するように工夫されているので、どの組織でいつ小胞体ストレスが起きているのかを簡便に 検出できる。実 際ERAIマウスは、薬剤による人為的な小胞体ストレスだけでなく、生理的条件下で自然に起こる小胞体ストレスをも鋭敏に検知するという新知見を得ることができた。ERAIマウスは、個体レベルにおける、発生・成熟・老化の研究や、タンパ ク質変成疾患病の解析に 非常に有用と考えられる。
    • Iwawaki, T., Kohno, K., and Miura, M. A transgenic mouse model for monitoring endoplasmic reticulum stress in vivo. Nat. Med. 10, 1014 (2004)
    上記論文( Nat. Med.10, 98-102)への質問に対する回答。

2003

  • Sano, H., Yasoshima, Y., Matsushita, N., Kaneko, T., Kohno, K., Pastan, I., and Kobayashi, K. Conditional ablation of striatal neuronal types containing dopamine D2 receptor disturbs coordination of basal ganglia function. J. Neurosci. 23, 9078-9088 (2003)
    IMCT法を用いて線条体特異的にドーパミンD2受容体を発現するニューロンを破壊することにより、D2受容体発現ニューロンの運動協調機能への生理的役割を解析した。この結果、線条体ー淡蒼球ニューロンは淡蒼球の抑制を介して自発運動を抑制し、ドーパミン刺激時には淡蒼球を脱抑制するとともに線条対ー黒質投射ニューロンに作用し運動促進作用を示すことが示唆された。
  • Kimata, Y., Kimata, Y. I., Shimizu, Y., Abe, H., Farcasanu, I. C., Takeuchi, M., Rose, MD., and Kohno, K. Genetic evidence for a role of BiP/Kar2 that regulates Ire1 in response to accumulation of unfolded proteins. Mol. Biol. Cell 14, 2559-2569 (2003)
    膜貫通型RNaseであるIre1の、小胞体ストレスに応じた活性調節において、小胞体内在性分子シャペロンであるBiPが負に寄与していることを、出芽酵母BiP遺伝子変異株を用いて証明した。
  • Kiso, S., Kawata, S., Tamura, S., Inui, Y., Yoshida, Y., Sawai, Y., Umeki, S., Ito, N., Yamada, A., Miyagawa, J., Higashiyama, S., Iwawaki, T., Saito, M., Taniguchi, N., Matsuzawa, Y., and Kohno, K. Liver regeneration in heparin-binding EGF-like growth factor transgenic mice after partial hepatectomy. Gastroenterology 124, 701-707 (2003)
    ヘパリン結合型EGF様増殖因子(HB-EGF)を肝実質細胞特異的に発現しているトランスジェニックマウスでは、野生型マウスに比べ肝切除後の肝細胞の DNA合成が促進されていることから、HB-EGFは肝実質細胞の増殖にin vivoで関わっていることが示唆された。
  • Ohdate, H., Lim, CR., Kokubo, T., Matsubara, K., Kimata, Y., and Kohno, K. Impairment of the DNA binding activity of the TATA-binding protein renders the transcriptional function of Rvb2p/Tih2p, the yeast RuvB-like protein, essential for cell growth. J. Biol. Chem. 278, 14647-14656 (2003)
    真核生物に共通して保存されているRuvB様ヘリカーゼであるTih1/Tih2複合体が、TATA-binding protein (TBP)と直接的に相互作用し、一部の遺伝子の転写に関与することを証明した。
  • Hosoda, A., Kimata, Y., Tsuru, A., and Kohno, K. JPDI, a novel endoplasmic reticulum-resident protein containing both a BiP-interacting J-domain and thioredoxin-like motifs. J. Biol. Chem. 278, 2669-2676 (2003)
    新規の小胞体内在性蛋白質として、JPDIを同定した。JPDIは、HSP70ファミリーシャペロンBiPと相互作用するJドメインと、ジスルフィド結合形成を促すと推測されるチオレドキシン様モチーフを併せ持つ。小胞体内腔での蛋白質折り畳みにおいて、新たな経路の存在が示唆される。

2002

  • Higashio, H., and Kohno, K. A genetic link between the unfolded protein response and vesicle formation from the endoplasmic reticulum. Biochem. Biophys. Res. Commun. 296, 568-574 (2002)
    小胞体からの小胞輸送を促すCOPIIコート蛋白質複合体構成因子と、小胞体ストレス応答シグナル伝達因子の間に強い遺伝学的相互作用が認められた。
  • Okushima, Y., Koizumi, N., Yamaguchi, Y., Kimata, Y., Kohno, K., and Sano, H. Isolation and characterization of a putative transducer of endoplasmic reticulum stress in Oryza sativa. Plant Cell Physiol. 43, 532-539 (2002)
    小胞体ストレス応答の情報伝達で重要な役割を果す受容型キナーゼ遺伝子をイネから単離し、 小胞体に局在すること、酵母でストレスセンサーとして機能することを示した。
  • Fujioka, Y., Kimata, Y., Nomaguchi, K., Watanabe, K., and Kohno, K. Identification of a novel non-structural maintenance of chromosomes (SMC) component of the SMC5-SMC6 complex involved in DNA repair. J. Biol. Chem. 277, 21585-21591 (2002)
    SMCファミリー蛋白質ヘテロダイマーSMC5/SMC6と複合体を形成して機能する蛋白質として、出芽酵母Nse1を同定した。NSE1遺伝子変異株の表現型解析により、SMC5/SMC6を中心とする複合体の、DNA修復における役割が確認された。

2001

  • Koizumi, N., Martinez, I., Kimata, Y., Kohno, K., Sano, H., and Chrispeels, MJ. Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum located transmembrane protein kinases. Plant Physiol. 127, 949-962 (2001)
  • Saito, M., Iwawaki, T., Taya, C., Yonekawa, H., Noda, M., Inui, Y., Mekada, E., Kimata, Y., Tsuru, A., and Kohno, K.Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat. Biotechnol. 19, 746-750 (2001)
    • Research Highlight: ; Srinivasan, J. Nat. Rev. Genet. 2, 654 (2001)
    • Press release: "Disease on demand" Nat. Biotechnol., August (2001)
    • News & Views: Palmiter, R; Interrogation by toxin. Nat. Biotechnol 19, 731-732 (2001)
    → 新聞記事
  • Iwawaki, T., Hosoda, A., Okuda, T., Kamigori, Y., Nomura-Furuwatari, C., Kimata, Y., Tsuru, A., and Kohno, K.Translational control by ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat. Cell Biol. 3, 158-164 (2001)
  • Lutz, W., Kohno, K., and Kumar, R. The role of heat shock protein 70 in vitamin D receptor function. Biochem. Biophys. Res. Commun. 282, 1211-1219 (2001)

2000

  • Iwawaki, T., Kohno, K., and Kobayashi, K. Identification of a potential Nurr1 response element that activates the tyrosine hydroxylase gene promoter in cultured cells. Biochem. Biophys. Res. Commun. 274, 590-595 (2000)
  • Kimata, Y., Ooboki, K., Nomura-Furuwatari, C., Hosoda, A., Tsuru, A., and Kohno, K. Identification of a novel mammalian endoplasmic reticulum-resident KDEL protein using an EST database motif search. Gene 261, 321-327 (2000)
  • Okamura, K., Kimata, Y., Higashio, H., Tsuru, A., and Kohno, K. Dissociation of Kar2p/BiP from an endoplasmic reticulum sensory molecule, Ire1p, triggers unfolded protein response in yeast. Biochem. Biophys. Res. Commun. 279, 445-450 (2000)
  • Lim, CR., Kimata, Y., Ohdate, H., Kokubo, T., Kikuchi, N., Horigome, T., and Kohno, K. The Saccharomyces cerevisiae RuvB-like protein, Tih2p is required for cell cycle progression. J. Biol. Chem. 275, 22409-22417 (2000)
  • Higashio, H., Kimata, Y., Kiriyama, T., Hirata, A., and Kohno, K. Sfb2p, a yeast protein related to Sec24p, can function as a constituent of COPII coats required for vesicle budding from the endoplasmic reticulum. J. Biol. Chem. 275, 17900-17908 (2000)
  • Kimata, Y., Higashio, H., and Kohno, K. Impaired proteasome function rescues thermosensitivity of yeast cells lacking the coatomer subunit epsilon-COP. J. Biol. Chem. 275, 10655-10660 (2000)
  • Yoshizawa, F., Miura, Y., Tsurumaru, K., Kimata, Y., Yagasaki, K., and Funabiki, R. Elongation factor 2 in the liver and skeletal muscle of mice is decreased by starvation. Biosci. Biotechnol. Biochem. 64, 2482-2485 (2000)

1999

  • Kimata, Y., Lim, CR., Kiriyama, T., Nara, A., Hirata, A., and Kohno, K. Mutation of the yeast ε-COP gene ANU2causes abnormal nuclear morphology and defects in intracellular vesicular transport. Cell Struct. Funct. 24, 197-208 (1999)
  • Shimada, A., Kato, S., Enjo, K., Osada, M., Ikawa, S., Kohno, K., Obinata, M., Kanamaru, R., and Ishioka, C. The transcriptional activities of p53 and its homologue-51: similarities and differences. Cancer Res. 12, 2781-2786 (1999)
  • Kohno, K., and Shimamoto, T. Nucleotide excision repair assay using established cell lines. Methods Mol. Biol. 113, 337-346 (1999) “DNA repair protocols. Eukaryotic systems” Ed. D. S. Henderson, Humana Press, Totowa, NJ, USA
  • Kikuchi, N., Gohshi, T., Kawahire, S., Tachibana, T., Yoneda, Y., Isobe, T., Lim, CR., Kohno, K., Ichimura, T., Omata, S., and Horigome, T. Molecular shape and ATP binding activity of rat p50, a putative mammalian homologue of RuvB DNA helicase. J. Biochem. 125, 487-494 (1999)
  • Kimata, Y., Lim, C. R., and Kohno, K. S147P GFP: a less thermosensitive green fluorescent protein variant. Methods Enzymol. 302, 373-378 (1999) “ Green Fluorescent Protein” ed. by P. M. Conn, Academic Press, San Diego, CA

1998

  • Hayashi, A., Ogawa, H., Kohno, K., Gasser, S. M., and Hiraoaka, Y. Dynamics of centromeres and telomeres during meiosis in yeast Saccharomyces cerevisiae. Genes Cells 3, 587-601 (1998)
  • Ogura, K., Kohno, K., and Tai, T. Molecular cloning of a rat brain cDNA, with homology to a tyrosine kinase substrate, that induces galactosylceramide expression in COS-7 cells. J. Neurochem. 71, 1827-1836 (1998)
  • Oka, M., Nakai, M., Endo, T., Lim, CR., Kimata, Y., and Kohno, K. Loss of Hsp70-Hsp40 chaperone activity causes abnormal nuclear distribution and aberrant microtubule formation in M-phase of Saccharomyces cerevisiae. J. Biol. Chem. 273, 29727-29737 (1998)
  • Ikeda, Y., Ashida, Y., Takagi, A., Fukuoka, T., Tsuru, A., Tsushima, M., and Yamamoto, A. Mechanism of the production of small dense LDL(sLDL) in hypertriglyceridemia. Atherosclerosis XI. 777-788 (1998)

1997

  • Kimata, Y., Iwaki, M., Lim, CR., and Kohno, K. A novel mutation which enhances the fluorescence of green fluorescent protein at high temperatures. Biochem. Biophys. Res. Commun. 232, 69-73 (1997)
  • Oka, M., Kimata, Y., Mori, K., and Kohno, K. Saccharomyces cerevisiae KAR2 (BiP) gene expression is induced by loss of cytosolic HSP70/Ssa1p through a heat shock element-mediated pathway. J. Biochem. 121, 578-584 (1997)
  • Iannuzzi, L., Hayes, H., Di Meo, G.P., Mercier, D., and Kohno, K. Chromosomal localization of alpha-galactosyltransferase 1 (GGTA1) and elongation factor 2 (EEF2) genes in river buffalo by FISH. Chromosome Res. 5, 274-276 (1997)

1996

  • Ogura, K., Nara, K., Watanabe, Y., Kohno, K., Tai, T., and Sanai, Y. Cloning and expression of cDNA for O-acetylation of GD3 ganglioside. Biochem. Biophys. Res. Commun. 225, 932-938 (1996)
  • Hayes, H., Le Chalony, C., Goubin, G., Mercier, D., Payen, E., Bignon, C., and Kohno, K. Localization of ZNF164, ZNF146, GGTA1, SOX2, PRLR and EEF2 on homoeologous cattle, sheep and goat chromosomes by fluorescent in situ hybridization and comparison with the human gene map. Cytogenet. Cell Genet. 72, 342-346 (1996)

1995

  • Shimamoto, T., Tanimura, T., Yoneda, Y., Kobayakawa, Y., Sugasawa, K., Hanaoka, F., Oka, M., Okada, Y., Tanaka, K., and Kohno, K. Expression and functional analyses of Dxpa gene, the Drosophila homolog of human excision repair gene XPA. J. Biol. Chem. 270, 22452-22459 (1995)
  • Lim, C. R., Kimata, Y., Oka, M., Nomaguchi, K., and Kohno, K. Thermosensitivity of green fluorescent protein fluorescence utilized to reveal novel nuclear-like compartments in a mutant nucleoporin NSP1. J. Biochem. 118, 13-17 (1995)

1994

  • Terada, N., Patel, H.R., Takase, K., Kohno, K., Nairn, A.N., and Gelfand, E.W. Rapamycin selectively inhibits translation of mRNAs encoding elongation factors and ribosomal proteins. Proc. Natl. Acad. Sci. USA 91, 11477-11481 (1994)
  • Kimata, Y. and Kohno, K. Elongation factor 2 mutants deficient in diphthamide formation show temperature-sensitive cell growth.J. Biol. Chem. 269, 13497-13501 (1994)

1993

  • Kimata, Y., Harashima, S., and Kohno, K. Expression of non-ADP-ribosylatable diphtheria toxin-resistant elongation factor 2 in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 191, 1145-1151 (1993)
  • Kohno, K., Normington, K., Sambrook, J., Gething, M.-J., and Mori, K. The promoter region of the yeast KAR2(BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum.Mol. Cell. Biol. 13, 877-890 (1993)

奈良先端科学技術大学院大学
研究推進機構 特別プロジェクトグループ
河野特任研究プロジェクト(旧:動物細胞工学研究室)