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Ubiquitination of overexpressed protein and enclosure by inducible ER membrane

Research Project

Project/Area Number 17590244
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

ODA Toshiaki  Hamamatsu Univ. 8ch. Medi., Associate Prot., 医学部, 准教授 (90126805)

Co-Investigator(Kenkyū-buntansha) KITAGAWA Masatoshi  Hamamatsu Univ. Sch. Med., Prof, 医学部, 教授 (50294971)
UCHIDA Chiharu  Hamamatsu Univ. Sch. Med., Assistant Prof, 医学部, 助教授 (60223567)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsprotein overexpression / crystalloid endoplasmic reticulum / organelle targeting signal / inducible ER / cell response / タンパク質過剰発現 / タンパク質過剰産生ストレス / タンパク質の質と量の制御 / ユビキチン化
Research Abstract

It has been reported that overexpression in the culture cells of endoplasmic reticulum (ER) membrane proteins, such as microsomal aldehyde dehydrogenase (ALDH), causes the induction of a specific ER membrane structure (crystalloid ER, cER). We recently found for the first time that overexpression of an ER-unrelated, mitochondrial precursor for serine : pyruvate aminotransferase (SPT45K) induced the generation of cER, and overexpressed pOTC and pAd, other mitochondrial precursor proteins, also induced the ER aggregates. We also found that the chimeric fluorescent protein having the C terminal ER targeting sequence of ALDH at the C terminus had the remarkable ER aggregating activity by the overexpression. Because these cER (or ER aggregates) inducing activities were not observed in the cases of proteins (SPT43K, ALDHdC, EYFP) lacking organelle targeting signals, the activities is dependent on their structures. It was further indicated that the cER (ER aggregates) inducing activities was dependent on their expression levels in the cell. These data suggest that the cell has a novel system for the detection of the quality (structure) and the quantity of proteins expressed in the cytoplasm by inducing the new ER membrane structure.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (34 results)

All 2007 2006 2005 Other

All Journal Article (34 results)

  • [Journal Article] Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice.2007

    • Author(s)
      Suzuki, S., Fukasawa, H., Kitagawa, K., Uchida, C., Hattori, T., Isobe, T., Oda, T., Misaki, T., Ohashi, N., Nakayama, K., Nakayama, K.I., Hishida, A., Yamamoto, T., Kitagawa M.
    • Journal Title

      Am. J. Pathol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice.2007

    • Author(s)
      Suzuki, S., Fukasawa, H., Kitagawa, K., Uchida, C., Hattori, T., Isobe, T., Oda, T., Misaki, T., Ohashi, N., Nakayama, K., Nakayama, K.I., Hishida, A., Yamamoto, T., Kitagawa, M.
    • Journal Title

      Am. J. Pathol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors : Sequential analyses2006

    • Author(s)
      Kikuchi, H., Yamashita, K., Kawabata, T., Yamamoto, M., Hiramatsu, Y., Kondo, K., Baba, M., Ohta, M., Kamiya, K., Tanaka, T., Suzuki, S., Kitagawa, K., Kitagawa, M., Sugimura, H., Konon, H.
    • Journal Title

      Cancer Sci 97

      Pages: 127-132

    • NAID

      10020388517

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia2006

    • Author(s)
      Kono, S., Suzuki, H., Oda, T., Miyajima, H., Takahashi, Y., Shirakawa, K., Ishikawa, K., Kitagawa, M.
    • Journal Title

      Neuromol. Med. 8

      Pages: 361-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of GPR48 induced by down-regulation of p27^<Kip1> enhances carcinoma cell invasiveness and metastasis2006

    • Author(s)
      Gao, Y., Kitagawa, K., Hiramatsu, Y., Kikuchi, H., Isobe, T., Shimada, M., Uchida, C., Hattori, T., Oda, T., Nakayama, K., Nakayama, K.I., Tanaka, T., Konno, H., Kitagawa, M.
    • Journal Title

      Cancer Res 66

      Pages: 11623-11631

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Degradation of Tob1 Mediated by SCF^<ska2>-Dependent Ubiquitination2006

    • Author(s)
      Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., Oda, T., Hatakeyama, S., Nakayama, KI., Yamamoto, T., Konno, H., Kitagawa M.
    • Journal Title

      Cancer Res 66

      Pages: 8477-8483

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury2006

    • Author(s)
      Fukasawa, H., Yamamoto, T., Togawa, A., Ohashi, N., Fujigaki, Y., Oda T., Uchida C., Kitagawa, K., Hattori, T., Suzuki, S., Kitagawa, M., Hishida
    • Journal Title

      Kidney Int 69

      Pages: 1733-1740

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of MdmX on Mdm2-mediated downregulation of pRB.2006

    • Author(s)
      Uchida, C., Miwa, S., Isobe, T., Kitagawa, K., Hattori, T., Oda, T., Yasuda, H., Kitagawa, M.
    • Journal Title

      FEBS Letters 560

      Pages: 1753-1758

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69.2006

    • Author(s)
      Isobe, T., Uchida, C., Hattori T., Kitagawa, K., Oda, T., Kitagawa, M.
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 367-374

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner2006

    • Author(s)
      Miwa, S., Uchida, C., Kitagawa, K., Hattori, T., Oda, T., Sugimura, H., Yasuda, H., Nakamura, H., Chida K., Kitagawa, M.
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 54-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor2006

    • Author(s)
      Gao, Y., Kitagawa, K., Shimada, M., Uchida, C., Hattori, T., Oda, T., Kitagawa.M.
    • Journal Title

      H. J. Med. Sci.(北海道医誌). 81

      Pages: 101-109

    • NAID

      10029919292

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors : Sequential analyses2006

    • Author(s)
      Kikuchi, H., Yamashita, K., Kawabata, T., Yamamoto, M., Hiramatsu, Y., Kondo, K., Baba, M., Ohta, M., Kamiya, K., Tanaka, T., Suzuki, S., Kitagawa, K., Kitagawa, M., Sugimura, H., Konno, H
    • Journal Title

      Cancer Sci. 97

      Pages: 127-132

    • NAID

      10020388517

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia2006

    • Author(s)
      Kono, S., Suzuki, H., Oda T., Miyajima, H., Takahashi, Y., Shirakawa, K., Ishikawa, K., Kitagawa, M
    • Journal Title

      Neuromol. Med. 8

      Pages: 361-374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of GPR48 induced by down-regulation of p27kip1 enhances carcinoma cell invasiveness and metastasis2006

    • Author(s)
      Gao, Y., Kitagawa, K., Hiramatsu, Y., Kikuchi, H., Isobe, T., Shimada, M., Uchida, C., Hattori, T., Oda, T., Nakayama, K., Nakayama, K.I., Tanaka, T., Konno, H., Kitagawa, M
    • Journal Title

      Cancer Res. 66

      Pages: 11623-11631

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Degradation of Tobl Mediated by SkP2-Dependent Ubiquitination2006

    • Author(s)
      Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., Oda T., Hatakeyama, S., Nakayama, KI., Yamamoto, T., Konno, H., Kitagawa M.
    • Journal Title

      Cancer Res. 66

      Pages: 8477-8483

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ubiqui tin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury2006

    • Author(s)
      Fukasawa, H., Yamamoto, T., Togawa, A., Ohashi, N., Fujigaki, Y., Oda, T., Uchida, C., Kitagawa, K., Hattori, T., Suzuki, S., Kitagawa, M., Hishida
    • Journal Title

      Kidney Int. 69

      Pages: 1733-1740

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of MdmX on Mdm2-ediated downregulation of pRB2006

    • Author(s)
      Uchida, C., Miwa, S., Isobe, T., Kitagawa, K., Hattori, T., Oda, T., Yasuda, H., Kitagawa, M.
    • Journal Title

      FEBS Letters 560

      Pages: 1753-1758

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69.2006

    • Author(s)
      Isobe, T., Uchida, C., Hattori, T., Kitagawa, K., Oda, T., Kitagawa, M
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 367-374

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner2006

    • Author(s)
      Miwa, S., Uchida C., Kitagawa, K., Hattori, T., Oda, T., Sugimura, H., Yasuda, H., Nakamura, H.Chida K., Kitagawa, M
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 54-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor2006

    • Author(s)
      Gao, Y., Kitagawa, K., Shimada, M., Uchida, C., Hattori, T., Oda, T., Kitagawa, M.
    • Journal Title

      H.J.Med.Sci(北海道医誌). 81

      Pages: 101-109

    • NAID

      10029919292

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors : Sequential analyses2006

    • Author(s)
      Kikuchi, H., Yamashita, K., Kawabata, T., Yamamoto, M., Hiramatsu, Y., Kondo, K., Baba, M., Ohta, M., Kamiya, K., Tanaka, T., Suzuki, S., Kitagawa, K., Kitagawa, M., Sugimura, H., Konno, H
    • Journal Title

      Cancer Sci 97

      Pages: 127-132

    • NAID

      10020388517

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Biochemical features of ceruloplasmin gene mutations linked to aceruloplasminemia2006

    • Author(s)
      Kono, S., Suzuki, H., Oda, T., Miyajima, H., Takahashi, Y., Shirakawa, K., Ishikawa, K., Kitagawa.M
    • Journal Title

      Neuromol. Med. 8

      Pages: 361-374

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Up-regulation of GPR48 induced by down-regulation of p27^<Kip1> enhances carcinoma cell invasiveness and metastasis2006

    • Author(s)
      Gao, Y., Kitagawa, K., Hiramatsu, Y., Kikuchi, H., Isobe, T., Shimada, M., Uchida.C., Hattori, T., Oda.T., Nakayama, K., Nakayama, K.I., Tanaka, T., Konno, H., Kitagawa.M
    • Journal Title

      Cancer Res 66

      Pages: 11623-11631

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Degradation of Tobl Mediated by SCF^<Skp2>-Dependent Ubiquitination2006

    • Author(s)
      Hiramatsu, Y., Kitagawa, K., Suzuki, T., Uchida, C., Hattori, T., Kikuchi, H., Oda, T., Hatakeyama, S., Nakayama, KI., Yamamoto, T., Konno, H., Kitagawa M.
    • Journal Title

      Cancer Res 66

      Pages: 8477-8483

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury2006

    • Author(s)
      Fukasawa, H., Yamamoto, T., Togawa, A., Ohashi, N., Fujigaki, Y., Oda, T., Uchida C., Kitagawa, K., Hattori, T., Suzuki, S., Kitagawa, M., Hishida
    • Journal Title

      Kidney Int 69

      Pages: 1733-1740

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Effects of MdmX on Mdm2-mediated downregulation of pRB.2006

    • Author(s)
      Uchida, C., Miwa, S., Isobe, T., Kitagawa, K., Hattori, T., Oda.T., Yasuda, H., Kitagawa.M.
    • Journal Title

      FEBS Letters 560

      Pages: 1753-1758

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69.2006

    • Author(s)
      Isobe, T., Uchida.C., Hattori, T., Kitagawa, K., Oda, T., Kitagawa, M
    • Journal Title

      Biochem Biophys Res Commun 339

      Pages: 367-374

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner2006

    • Author(s)
      Miwa, S., Uchida, C., Kitagawa, K., Hattori, T., 0da, T., Sugimura, H., Yasuda, H., Nakamura, H., Chida K., Kitagawa, M
    • Journal Title

      Biochem Biophys Res Commun 340

      Pages: 54-61

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein-coupled receptor2006

    • Author(s)
      Gao, Y., Kitagawa, K., Shimada, M., Uchida, C., Hattori, T., Oda, T., Kitagawa, M.
    • Journal Title

      H. J. Med. Sci(北海道医誌). 81

      Pages: 101-109

    • NAID

      10029919292

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner.2006

    • Author(s)
      Miwa, S., Uchida, C., Kitagawa, K., Hattori, T., Oda, T., Sugimura, H., Yasuda, H., Nakamura, H., Chida K., Kitagawa, M.
    • Journal Title

      Biochem Biophys Res Commun. 340

      Pages: 54-61

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ubiquitin-dependent degradation of adenovirus E1A protein is inhibited by BS69.2006

    • Author(s)
      Isobe, T., Uchida, C., Hattori, T., Kitagawa, K., Oda, T., Kitagawa, M.
    • Journal Title

      Biochem Biophys Res Commun. 339

      Pages: 367-374

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transcriptional induction of Smurf2 ubiquitin ligase by TGF-b.2005

    • Author(s)
      Ohashi, N., Yamamoto, T., Uchida, C., Togawa, A., Fukasawa, H., Fujigaki, Y., Suzuki, S., Kitagawa, K., Hattori, T., Oda, T., Hayashi, H., Hishida, A., Kitagawa, M
    • Journal Title

      FEBS Letters 579

      Pages: 2557-2563

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced Mdm2 activity ibhibits pRB function via ubiquitin-dependent degradation.2005

    • Author(s)
      Uchida C., Miwa S., Kitagawa K., Hattori T., Isobe T., Otani S., Oda T., Sugimura H., Kamijo T., Ookawa K., Yasuda H., Kitagawa M.
    • Journal Title

      EMBO J. 24

      Pages: 160-169

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury.

    • Author(s)
      Fukasawa, H., Yamamoto, T., Togawa, A., Ohashi, N., Fujigaki, Y., Oda, T., Uchida, C., Kitagawa, K., Hattori, T., Suzuki, S., Kitagawa, M., Hishida, A
    • Journal Title

      Kidney Int. (in press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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