2004 Fiscal Year Final Research Report Summary
Studies on proteolysis mediated by the proteasomes and ubiquitin
Project/Area Number |
13002008
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Research Category |
Grant-in-Aid for Specially Promoted Research
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Tokyo Metropolitan Organization for Medical Research |
Principal Investigator |
TANAKA Keiji the tokyo metropolitan institute of medical science, the tokyo metropolitan institute of medical science, Acting Director, 東京都臨床医学綜合研究所, 参事研究員 (10108871)
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Co-Investigator(Kenkyū-buntansha) |
YASHIRODA Hideki The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (20311425)
YOSHIDA Yukiko The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (90271543)
MURATA Shigeo The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (20344070)
KOMATSU Masaaki The Tokyo Metropolitan, Institute of Medical Science, Researcher, 東京都臨床医学綜合研究所, 研究員 (90356254)
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Project Period (FY) |
2001 – 2005
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Keywords | enzyme / signal transduction / stress / protein / neurodegenerative diseases / proteasome / ubiquitin |
Research Abstract |
The proteasome (a eukaryotic ATP-dependent protease complex) is a sophisticated cellular apparatus capable of shredding unnecessary proteins modified by ubiquitin (a posttranslational modifier serving a destination signal for proteolysis) selectively. It plays a central role in the control of a diverse array of cellular activities by catalyzing biological reactions rapidly, orderly, exhaustively, and uni-directionally. Over the past 25 years, we have been aiming to elucidate comprehensively the divergent roles of the ubiquitin-proteasome system (UPS) in the life science field. In the present project named "Studies on proteolysis mediated by the proteasomes and ubiquitin", our research projects on the proteasomes were (1) the analysis of the tertiary structure of the mammalian proteasome as a unusually large multi-protein complex, (2) the clarification of assembling mechanisms, focusing on the newly-discovered PAC (proteasome assembling chaperone) 1/2 heterodimeric complex and Hsp90, and (3) immunogenetic analysis of the new proteasome activator family proteins of PA28α, PA28β and PA28γ. In the ubiquitin project, we were interested in analyzing the quality-control ubiquitin-protein ligases (E3s) in cells: CHIP is a molecular chaperone-dependent E3, Parkin is encoded by the causative gene of eating of oneself") and two novel ubiquitin-like (UBL) modifying systems, such as NEDD8 and Ufml pathways, by generation of model mice with impairment of various related genes. Recently, various diseases, such as cancers, infectious diseases, and neurodegenerative diseases, have been increasing in the aged society of the 21st century. Considering such circumstances, it has been clarified, as a central scenario, that dysfunctioning of UPS causes these intractable diseases. Thus, our studies may contribute to the development of new bio-science field as well as to that of therapies for intractable diseases.
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Research Products
(36 results)
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[Journal Article] 14-3-3h is a novel regulator of parkin ubiquitin-ligase2006
Author(s)
Sato, S., Chiba, T., Sakata, E., Kato, K., Mizuno, Y., Hattori, N, Tanaka, K
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Journal Title
EMBO J. 25
Pages: 211-221
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Diverse effects of pathogenic mutations of Parkin that catalyzes multiple mono-ubiquitylation in vitro2006
Author(s)
Matsuda, N., Kitami, T., Suzuki, T., Mizuno, Y., Hattori, N., Tanaka, K.
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Journal Title
J. Biol. Chem. 281
Pages: 3204-3209
Description
「研究成果報告書概要(和文)」より
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[Journal Article] 14-3-3h is a novel regulator of parkin ubiquitin-ligase2006
Author(s)
Sato, S., Chiba, T., Sakata, E., Kato, K., Mizuno, Y., Hattori, N, Tanaka, K.
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Journal Title
EMBO J. 25
Pages: 211-221
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes2005
Author(s)
Hirano, Y., Hendil, K.B., Yashiroda, H., Iemura, S., Nagane, R., Hioki, Y., Natsume, T., Tanaka, K., Murata, S.
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Journal Title
Nature 437
Pages: 1381-1385
Description
「研究成果報告書概要(和文)」より
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[Journal Article] DDB2, the xeroderma pigmentosum group E gene product, is directly ubiquitylated by Cullin 4A-based ubiquitin ligase complex2005
Author(s)
Matsuda, N., Azuma, K., Saijo, M., Iemura, S-I., Hioki, Y., Natsume, T., Chiba, T., Tanaka, K., Tanaka, K.
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Journal Title
DNA Repair 4
Pages: 537-545
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice2005
Author(s)
Komatsu, M., Waguri, S., Ueno, T., Murata, S., Tanida, I., Ezaki, E., Mizushima, N., Ohsumi, Y., Uchiyama, Y., Kominami, E., Tanaka, K., Chiba, T.
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Journal Title
J. Cell Biol. 169
Pages: 425-434
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Impairment o starvation-induced and constitutive autophagy in Atg7-deficient mice2005
Author(s)
Komatsu, M., Waguri, S., Ueno, T., Murata, S., Tanida, I., Ezaki, E., Mizushima, N., Ohsumi, Y., Uchiyama, Y., Kominami, E., Tanaka, K., Chiba, T.
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Journal Title
J. Cell Biol. 169
Pages: 425-434
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Structural basis of sugar-recognizing ubiquitin ligase2004
Author(s)
Mizushima, T., Hirao, T., Yoshida, Y., Lee, S.J., Chiba, T., Iwai, K., Yamaguchi, Y., Kato, K., Tsukihara, T., Tanaka, K.
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Journal Title
Nature Struct. Mol. Biol. 11
Pages: 365-370
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A novel protein-conjugating system for Ufml, a ubiquitin-fold modifier2004
Author(s)
Komatsu, M., Chiba, T., Tatsumi, K., Iemura, S., Tanida, I., Okazaki, N., Ueno, T., Kominami, E., Natsume, T., Tanaka, K.
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Journal Title
EMBO J. 23
Pages: 1977-1986
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A novel protein-conjugating system for Ufml, a ubiquitin-fold modifier2004
Author(s)
Komatsu, M., Chiba, T., Tatsumi, K., Iemura, S., Tanida, I., Okazaki, N., Ueno, T., Kominami, E., Natsume, T., Tanaka, K..
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Journal Title
EMBO J. 23
Pages: 1977-1986
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Parkin binds the Rpn10 subunit of 26S proteasomes with the ubiquitin-like domain2003
Author(s)
Sakata, E., Yamaguchi, Y., Kurimoto, E., Kikuchi, J., Yokoyama, S., Yamada, S., Kawahara, H., Yokosawa, H., Hattori, N., Mizuno, Y., Tanaka, K., Kato, K.
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Journal Title
EMBO Rep. 4
Pages: 301-306
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Fbs2 is a new member of the E3 ubiquitin ligase family that recognizes sugar chains2003
Author(s)
Yoshida, Y., Tokunaga, F., Chiba, T., Iwai, K., Tanaka, K., Tai, T.
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Journal Title
J. Biol. Chem. 278
Pages: 43877-43884
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Parkin binds the Rpn10 subunit of 26S proteasomes with the ubiquitin-like domain2003
Author(s)
Sakata, E., Yamaguchi, Y., Kurimoto, E., Kikuchi, J., Yokoyama, S., Yamada, S., Kawahara, H., Yokosawa, H., Hattori, N.Mizuno, Y., Tanaka, K., Kato, K.
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Journal Title
EMBO Rep 4
Pages: 301-306
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The structure of the mammalian 20S proteasome at 2.75 Å resolution2002
Author(s)
Unno, M., Mizushima, T., Morimoto, Y., Tomisugi, Y., Tanaka, K., Yasuoka, N., Tsukihara, T.
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Journal Title
Structure 10
Pages: 609-618
Description
「研究成果報告書概要(和文)」より
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[Journal Article] E3 ubiquitin-ligase that recognizes sugar chains2002
Author(s)
Yoshida, Y., Chiba, T., Tokunaga, T., Kawasaki, H., Iwai, K., Suzuki, T., Ito, Y., Matsuoka, K., Yoshida, M., Tanaka, K., Tai, T.
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Journal Title
Nature 418
Pages: 438-442
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Two distinct pathways mediated by PA28 and hsp90 in MHC class I antigen processing2002
Author(s)
Yamano, T., Murata, S., Shimbara, N., Tanaka, N., Chiba, T., Tanaka, K., Yui, K., Udono, H.
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Journal Title
J. Exp. Med. 196
Pages: 185-196
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The structure of the mammalian 20S proteasome at 2.75Å resolution2002
Author(s)
Unno, M., Mizushima, T., Morimoto, Y., Tomisugi, Y., Tanaka, K., Yasuoka, N., Tsukihara, T.
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Journal Title
Structure 10
Pages: 609-618
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Two distinct pathways mediated by PA28 and hsp90 in MHC class I antigen processing2002
Author(s)
Yamano, T., Murata, S., Shimbara, N., Tanaka, N., Chiba, T., Tanaka, K.Yui, K., Udono, H.
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Journal Title
J. Exp. Med. 196
Pages: 185-196
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] NEDD8 recruits E2-ubiquitin to SCF E3-ligase2001
Author(s)
Kawakami, T., Chiba, T., Suzuki, T., Iwai, K., Yamanaka, K., Minato, N., Hidaka, Y., Shimbara, N., Suzuki, H., Osak, F., Omata, M., Tanaka, K
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Journal Title
EMBO J. 20
Pages: 4003-4012
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Immunoproteasome assembly and antigen processing in mice lacking both PA28a and PA28b2001
Author(s)
Murata, S., Udono, H., Tanahashi, N., Hamada, N., Adachi, K., Yamano, T., Yui, K., Kobayashi, N., Kasahara, M., Tanaka, K., Chiba, T.
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Journal Title
EMBO J 20
Pages: 5898-5907
Description
「研究成果報告書概要(和文)」より
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[Journal Article] NEDD8 recruits E2-ubiquitin to SCF E3-ligase2001
Author(s)
Kawakami, T., Chiba, T., Suzuki, T., Iwai, K., Yamanaka, K., Minato, N., Hidaka, Y., Shimbara, N., Suzuki, H., Osak, F., Omata, M., Tanaka, K.
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Journal Title
EMBO J. 20
Pages: 4003-4012
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immunoproteasome assembly and antigen processing in mice lacking both PA28a and PA28b.2001
Author(s)
Murata, S., Udono, H., Tanahashi, N., Hamada, N., Adachi, K., Yamano, T., Yui, K., Kobayashi, N., Kawahara, M., Tanaka, K., Chiba, T.
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Journal Title
EMBO J. 20
Pages: 5898-5907
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Loss of autophagy in the central nervous system causes neurodegeneration
Author(s)
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., Tanaka, K
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Journal Title
Nature (Published online 19 April 2006, doi : 10.1038/nature 04723). (in press)
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Loss of autophagy in the central nervous system causes neurodegeneration
Author(s)
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., Tanaka, K.
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Journal Title
Nature (in press)(Published online 19 April 2006, doi:10.1038/ nature 04723).
Description
「研究成果報告書概要(欧文)」より
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[Book] Ubiquity and diversity of the proteasome system. In " Protein Degradation"(Eds. By Mayer, R. J., Ciechanover, A., and Rechsteiner, M.)2006
Author(s)
Tanaka, K., Yashiroda, H., Murata, S.
Total Pages
129-156
Publisher
Wiley-VCH Verlag GmbH, Weinheim, Germany
Description
「研究成果報告書概要(和文)」より
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