Mechanisms of remodeling and quality control of proteins by AAA chaperones

2011 Fiscal Year Final Research Report

• Project Area: Protein community: organization and maintenance of protein functions
• Project/Area Number: 19058012
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kumamoto University
• Principal Investigator: OGURA Teru 熊本大学, 発生医学研究所, 教授 (00158825)
• Co-Investigator(Kenkyū-buntansha): YAMANAKA Kunitoshi 熊本大学, 発生医学研究所, 准教授 (90212290) ; ESAKI Masatoshi 熊本大学, 発生医学研究所, 助教 (70437911)
• Project Period (FY): 2007 – 2011
• Keywords: AAA タンパク質 / 分子シャペロン / ATPase / 線虫 / 酵母 / 神経変性疾患

Research Abstract

Systematic analysis uncovered the mechanism common to several AAA chaperones. The importance of cooperativity of the ATPase activity of D2 in p97/VCP/CDC-48/Cdc48p has been demonstrated. High-speed atomic force microscopy revealed repeated rotational movements of the p97 ring in the presence of ATP. Using yeasts and nematodes, cellular and developmental roles of AAA chaperones such as p97, fidgetin, and Bcs1p were elucidated. These results shed light on the molecular mechanisms of human diseases related to these AAA chaperones.

Research Products

• [Journal Article] Recent advances in p97/VCP/Cdc48 cellular functions. (2012)
  • Author(s): Yamanaka, K., Sasagawa, Y., and Ogura, T.
  • Journal Title: Biochim. Biophys. Acta Volume: 1823 Pages: 130-137
  • DOI: doi:10.1016/j.bbamcr.2011.07.001
  • Peer Reviewed
• [Journal Article] Positive cooperativity of the p97 AAA ATPase is critical for essential functions. (2011)
  • Author(s): Nishikori, S., Esaki, M., Yamanaka, K., Sugimoto, S., and Ogura, T.
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 15815-15820
  • DOI: doi:10.1074/jbc.M110.201400
  • Peer Reviewed
• [Journal Article] C. elegans UBX cofactors for CDC-48/p97 control spermatogenesis. (2010)
  • Author(s): Sasagawa, Y., Yamanaka, K. Saito-Sasagawa, Y., and Ogura, T.
  • Journal Title: Genes Cells 15 Pages: 1201-1215
  • DOI: doi:10.1111/j.1365-2443.2010.01454.x
  • Peer Reviewed
• [Journal Article] FtsH cleavage of non-native conformations of proteins. (2010)
  • Author(s): Ayuso-Tejedor, S., Nishikori, S., Okuno, T., Ogura, T., and Sancho, J.
  • Journal Title: J. Struct. Biol. Volume: 171 Pages: 117-124
  • DOI: doi:10.1016/j.jsb.2010.05.001
  • Peer Reviewed
• [Journal Article] High-speed atomic force microscopy techniques for observing dynamic biomolecular processes. (2010)
  • Author(s): Yamamoto, D., Uchihashi, T., Kodera, N., Yamashita, H., Nishikori, S., Ogura, T., Shibata, M., and Ando, T.
  • Journal Title: Methods Enzymol. Volume: 475 Pages: 541-564
  • DOI: doi:10.1016/S0076-6879(10)75020-5
• [Journal Article] AAA+ chaperone ClpX regulates dynamics of prokaryotic cytoskeletal protein FtsZ. (2010)
  • Author(s): Sugimoto, S., Yamanaka, K., Nishikori, S., Miyagi, A., Ando, T., and Ogura, T.
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 6648-6657
  • DOI: doi:10.1074/jbc.M109.080739
  • Peer Reviewed
• [Journal Article] ATP-bound form of the D1 AAA domain inhibits an essential function of Cdc48p/p97. (2010)
  • Author(s): Esaki, M., and Ogura, T.
  • Journal Title: Biochem. Cell Biol. Volume: 88 Pages: 109-117
  • DOI: doi:10.1139/O09-116
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans p97 controls germline-specific sex determination by controlling TRA-1 level in a CUL-2-dependent manner. (2009)
  • Author(s): Sasagawa, Y., Otani, M., Higashitani, N., Higashitani, A., Sato, K., Ogura, T., and Yamanaka, K.
  • Journal Title: J. Cell Sci. Volume: 122 Pages: 3663-3672
  • DOI: doi:10.1242/jcs.052415
  • Peer Reviewed
• [Journal Article] Conserved aromatic and basic amino acid residues in the pore region of C. elegans spastin play critical roles in microtubule-severing. (2009)
  • Author(s): Matsushita-Ishiodori, Y., Yamanaka, K., Hashimoto, H., Esaki, M., and Ogura, T.
  • Journal Title: Genes Cells Volume: 14 Pages: 925-940
  • DOI: doi:10.1111/j.1365-2443.2009.01320.x
  • Peer Reviewed
• [Journal Article] p97 homologs from C. elegans, CDC-48.1 and CDC-48.2, suppress the aggregate formation of huntingtin exon1 containing expanded polyQ repeat. (2008)
  • Author(s): Nishikori, S., Yamanaka, K., Sakurai, T., Esaki, M., and Ogura, T.
  • Journal Title: Genes Cells Volume: 13 Pages: 827-838
  • DOI: doi:10.1111/j.1365-2443.2008.01214.x
  • Peer Reviewed
• [Journal Article] Involvement of HMG-12 and CAR-1 in the cdc-48.1 expression of Caenorhabditis elegans. (2008)
  • Author(s): Yamauchi, S., Higashitani, N., Otani, M., Higashitani, A., Ogura, T., and Yamanaka, K.
  • Journal Title: Dev. Biol. Volume: 318 Pages: 348-359
  • DOI: doi:10.1016/j.ydbio.2008.02.057
  • Peer Reviewed
• [Journal Article] From the common molecular basis of the AAA protein to various energy-dependent and -independent activities of AAA proteins. (2008)
  • Author(s): Ogura, T., Matsushita-Ishiodori, Y., Johjima, A., Nishizono, M., Nishikori, S., Esaki, M., and Yamanaka, K.
  • Journal Title: Biochem. Soc. Trans. Volume: 36 Pages: 68-71
  • DOI: doi:10.1042/BST0360068
  • Peer Reviewed
• [Journal Article] ER E3 ubiquitin ligase HRD-1 and its specific partner chaperone BiP play important roles in ERAD and developmental growth in C. Elegans. (2007)
  • Author(s): Sasagawa, Y., Yamanaka, K., and Ogura, T.
  • Journal Title: Genes Cells Volume: 12 Pages: 1063-1073
  • DOI: doi:10.1111/j.1365-2443.2007.01108.x
  • Peer Reviewed
• [Journal Article] The C. elegans homologue of the spastic paraplegia protein, spastin, disassembles microtubules. (2007)
  • Author(s): Matsushita-Ishiodori, Y., Yamanaka, K., and Ogura, T.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 359 Pages: 157-162
  • DOI: doi:10.1016/j.bbrc.2007.05.086
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans p97/CDC-48 is crucial for progression of meiosis I. (2007)
  • Author(s): Sasagawa, Y., Yamanaka, K., Nishikori, S., and Ogura, T.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 358 Pages: 920-924
  • DOI: doi:10.1016/j.bbrc.2007.05.022
  • Peer Reviewed
• [Journal Article] Differential expression pattern of UBX family genes in Caenorhabditis elegans. (2007)
  • Author(s): Yamauchi, S., Sasagawa, Y., Ogura, T., and Yamanaka, K.
  • Journal Title: Biochem. Biophys. Res. Commun. Volume: 358 Pages: 545-552
  • DOI: doi:10.1016/j.bbrc.2007.04.163
  • Peer Reviewed
• [Journal Article] C. elegans RBX-2-CUL-5- and RBX-1-CUL-2- based complexes are redundant for oogenesis and activation of the MAP kinase MPK-1. (2007)
  • Author(s): Sasagawa, Y., Sato, S., Ogura, T., and Higashitani, A.
  • Journal Title: FEBS Lett. Volume: 581 Pages: 145-150
  • DOI: doi:10.1016/j.febslet.2006.12.009
  • Peer Reviewed
• [Journal Article] Caenorhabditis elegans fidgetin homolog FIGL-1, a nuclear-localized AAA ATPase, binds to SUMO.
  • Author(s): Onitake, A., Yamanaka, K., Esaki, M., and Ogura, T.
  • Journal Title: J. Struct. Biol. Volume: (in press)
  • DOI: doi:10.1016/j.jsb.2012.04.022
  • Peer Reviewed
• [Journal Article] Cdc48p/p97-mediated regulation of mitochondrial morphology is Vms1p independent.
  • Author(s): Esaki, M., and Ogura, T.
  • Journal Title: J. Struct. Biol. Volume: (in press)
  • DOI: doi:10.1016/j.jsb.2012.04.017
  • Peer Reviewed
• [Journal Article] The C-terminal -helix of SPAS-1, a Caenorhabditis elegans spastin homologue, is crucial for microtubule severing.
  • Author(s): Onitake, A., Matsushita-Ishiodori, Y., Johjima, A., Esaki, M., Ogura, T., and Yamanaka, K.
  • Journal Title: J. Struct. Biol. Volume: (in press)
  • DOI: doi:10.1016/j.jsb.2012.04.010
  • Peer Reviewed
• [Presentation] Multiple aspects of multifunctional p97. (2011)
  • Author(s): Ogura, T., Noi, K., Arita-Morioka, K., Esaki, M., Murayama, Y., and Yamanaka, K.
  • Organizer: 9th International Conference on AAA Protein
  • Place of Presentation: 熊本市国際交流会館, Kumamoto, Japan.
  • Year and Date: 20111106-11
• [Presentation] Involvement of C. elegans p97-cofactor complexes in sex determination. (2010)
  • Author(s): Yamanaka, K., Sasagawa, Y., Murayama, Y., and Ogura, T.
  • Organizer: The 3rd International Symposium on Protein Community
  • Place of Presentation: ホテル日航奈良, Nara, Japan
  • Year and Date: 20100913-16
• [Presentation] Roles of p97, a multifunctional AAA chaperone, in C. elegans development. (2010)
  • Author(s): Ogura. T.
  • Organizer: Academia Sinica-Kumamoto University Joint Conference on Organogenesis, B1C Auditorium, Institute of Biomedical Sciences, Academia Sinica
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 20100408-09
• [Presentation] C. elegans CDC-48/p97 controls germline-specific sex determination. (2010)
  • Author(s): Yamanaka, K., Sasagawa, Y., and Ogura, T.
  • Organizer: BIT Life Sciences' 3rd Annual Protein and Peptide Conference (PepCon-2010)
  • Place of Presentation: Beijing, China
  • Year and Date: 20100321-23
• [Presentation] Molecular mechanisms of homologs of spastin and p97/VCP related to human genetic disorders. (2009)
  • Author(s): Ogura, T., Matsushita-Ishiodori, Y., Yamanaka, K., Nishikori, S., and Esaki, M.
  • Organizer: 8th International Conference on AAA Proteins
  • Place of Presentation: Toronto, Canada
  • Year and Date: 20090712-16
• [Presentation] Roles of p97/VCP, a multifunctional AAA chaperone, in protein oligomerization and aggregation in neurodegenerative diseases. (2009)
  • Author(s): Ogura, T., Nishikori, S., Yamanaka, K., and Esaki, M.
  • Organizer: BIT Life Sciences' 2_<nd> Annual Protein and Peptide Conference (PepCon-2009)
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 20090402-04
• [Presentation] From common molecular basis of the AAA ATPase to various energy-dependent and independent activities of AAA proteins. (2007)
  • Author(s): Ogura, T.
  • Organizer: The 7th International conference on AAA proteins
  • Place of Presentation: Royal Agricultural College, Cirencester, UK.
  • Year and Date: 20070909-13
• [Book] FtsH protease, a eubacterial membrane-bound AAA protease. In ATP-dependent proteases (Research Signport, ed. E. Kutejova) pp.87-114 (2008)
  • Author(s): Okuno, T., and Ogura, T.
• [Book] FtsH protease-mediated regulation of various cellular functions., In General and regulatory proteolysis. D. A. Dougan (ed.)
  • Author(s): Okuno, T., and Ogura, T.
  • Publisher: Springer SBM (in press)
• [Book] FtsH protease. In Handbook of Proteolytic Enzymes, 3rd edition, N. Rawlings and G. Salvesen(ed)
  • Author(s): Ogura, T., Okuno, T., Suno, R., and Akiyama, Y.
  • Publisher: Elsevier Ltd., (in press)
• [Remarks]
  • URL: http://www.imeg.kumamoto-u.ac.jp/divisions/molecular_cell_biology/
• [Remarks]
  • URL: http://mukb.medic.kumamoto-u.ac.jp/fukusei/index.html
• [Remarks]
  • URL: http://mukb.medic.kumamoto-u.ac.jp/AAA/aaainfo.html