Professor Kazuhiro Nagata

Area and Subject Taught Molecular and Cellular Biology
Research Theme(s) (1) Life of Proteins: Protein Quality Control Mechanism and Diseases
(2) Regulation of Cellular Functions by Molecular Chaperones
Academic Degrees Ph.D. (Kyoto Univ., D. Sc.)
Keywords for Research Field TMolecular chaperones, protein quality control
Office Phone Number 81-75-705-3090

Research Overview

The most important player for vital activity is the protein. After translation, proteins should be correctly folded by the aid of various molecular chaperones, resulting in acquiring the correct conformation and the authentic functions. When cells suffer from various cellular stresses, proteins are misfolded, which often causes various neurodegenerative diseases including Alzheimer’s disease. Cells have acquired protective mechanisms for such adverse conditions, which is called as protein quality control (PQC) mechanism. We have found and cloned several key molecules involved in such PQC mechanism. We are proceeding the studies elucidating the molecular mechanism for the selective degradation of misfolded proteins in the cells. Based on the background of cell biology, we are performing our studies by adopting various technologies including biochemistry, molecular biology, developmental biology and structural biology. We stick our research almost solely on the proteins that we found and cloned by ourselves, which we expect to help us to provide the novel concepts on this fi eld.

Notable Publications and Works in the Last Three Years

  1. S. Ito, K. Ogawa, K. Takeuchi, M. Takagi, M. Yoshida, T. Hirokawa, S. Hirayama, K. Shin-Ya, I. Shimada, T. Doi, N. Goshima, T.Natsume, K. Nagata:
    A small-molecule compound inhibits a collagen-specific molecular chaperone and could J.Biol. Chem. 292: 20076-20085(2017)
  2. R. Ushioda, A. Miyamoto, M. Inoue, S. Watanabe, M. Okumura, K. Maegawa, K. Uegaki, S.i Fujii, Y. Fukuda, M. Umitsu, J. Takagi, K. Inaba, K. Mikoshiba, K. Nagata:
    Redox-assisted regulation of Ca2+ homeostasis in the endoplasmic reticulum by disulfide reductase ERdj5
    Proc. Natl. Acad. Sci. USA, 113 (41): E6055-E6063 (2016)
  3. Y. Ishikawa, S. Ito, K. Nagata, L. Y. Sakai, H. Bachinger:
    Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules
    Proc. Natl. Acad. Sci. USA, 113 (41): E6936-E6044 (2016)
  4. S. Ito, K. Nagata
    Mutanis of collagen-specific molecular chaperone Hsp47 causing osteogenesis imperfecta are structurally unstable with weak binding affinity to collagen
    Biochem Biophys Res Commun, 469 (3): 437-442 (2016)
  5. Kotani Y, Morito D, Yamazaki S, Ogino K, Kawakami K, Takashima S, Hirata H, Nagata K.
    Neuromuscular regulation in zebrafish by a large AAA+ ATPase/ubiquitin ligase, mysterin/RNF213
    Scientific Reports 5:16161(2015)
  6. J. Kirstein-Miles, D. Morito, T. Kakihana, M. Sugihara, A. Minnen, S.M. Hipp, C. Nussbaum-Krammer, U.F. Hartl, K. Nagata, R.I.Morimoto:
    Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments.
    EMBO J. 34(18):2334-2349(2015)
  7. D. Morito & K. Nagata
    Pathogenic Hijacking of ER-Associated Degradation: Is ERAD Flexible ?
    Mol Cell. 59:335-344(2015)