Molecular and Cellular Biology

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Three groups are working on the following researches: 1) Quality control mechanism of proteins in mammalian cells, that ensures the correct folding of newly synthesized proteins and the intracellular degradation of misfolded polypeptides to maintain integrative cellular function and to avoid cellular insults, 2) Gene regulation mechanism using RNA aptamer, and 3) The process of T cell receptor β chain (TCRβ) gene rearrangement, using various methods based on molecular biology, cellular biology, immunology, biochemistry, and structural biology.

Research and Education

1) Cells are equipped with a sophisticated mechanism of quality control of proteins to maintain cellular functions. We are working on the molecular mechanism of ERQC (endoplasmic reticulum quality control) and ERAD (ER-associated degradation) in mammals, by focusing on the function of molecular chaperone proteins and lectins. ERAD of misfolded proteins and the disruption of ERQC are related with some genetic diseases and neurodegenerative disorders.
2) To analyze the gene regulation in vivo, we introduce an RNA aptamer as a specific inhibitor on the spot. Using this feature, we focus on three major issues. ① Architecture of transcription complex. ② The effect of chromatin remodeling factors on the transcription. ③ Establishment of new evaluation system and application of RNA aptamer.
3) We have tried to reveal how TCRβ gene rearrangement proceeds by analyzing TCRβ locus of murine thymic lymphomas. In vivo generation of T cells expressing two TCRβ chains is largely inhibited. However, we have shown that the regulation is not so strict at the level of gene rearrangement.

Figure1(細胞機能 )130329Scheme on the protein quality control mechanism in the endoplasmic reticulum (ER).

r-082-2EDEM3 (Endoplasmic reticulum-degradation enhancing -mannosidase-like protein-3) localizes in the ER.


Recent Publications

1. Fujimori, T., Kamiya, Y., Nagata, K., Kato K. and Hosokawa, N. (2013) Endoplasmic reticulum lectin XTP3-B inhibits endoplasmic reticulum-associated degradation of a misfolded α1-antitrypsin variant. FEBS J.: 280, 1563-1575
2. Iida, Y., Fujimori, T., Okawa, K., Nagata, K., Wada, I. and Hosokawa, N. (2011) SEL1L protein critically determines the stability of the HRD1-SEL1L endoplasmic reticulum-associated degradation (ERAD) complex to optimize the degradation kinetics of ERAD substrates. J. Biol. Chem. 286, 16929-16939
3. Hosokawa, N., Kato, K. and Kamiya, Y. (2010) Mannose 6-phosphate receptor homology domain-containing lectins in mammalian endoplasmic reticulum-associated degradation. Methods in Enzymology: 480 (Ed. M. Fukuda) Elsevier, 181-197
4. Hosokawa, N., Tremblay, L. O., Sleno, B., Kamiya, Y., Wada, I., Kato, K., Nagata, K. and Herscovics, A. (2010) EDEM1 accelerates the trimming of α1,2-linked mannose on the C branch of N-glycans. Glycobiology: 20, 567-575
5. Hirano, S., Kakinuma, S., Amasaki, Y., Nishimura, M., Imaoka, T., Fujimoto, S., Hino, O. and Shimada, Y. (2013) Ikaros is a critical target during simultaneous exposure to X-rays and N-ethyl-N-nitrosourea in mouse T-cell lymphomagenesis. Int. J. Cancer 132, 259-268.

Laboratory

Associate Professor:Nobuko Hosokawa
TEL: +81-75-751-3849
FAX: +81-75-751-4646
e-mail: nobukoh@frontier.kyoto-u.ac.jp
URL: http://www.frontier.kyoto-u.ac.jp/bf01/j/home.html
Lecturer:Kazunori Hirayoshi
TEL: +81-75-751-3840
e-mail: ippou@frontier.kyoto-u.ac.jp
Assistant Professor:Shinji Fujimoto
TEL: +81-75-751-3845
e-mail: fujimoto@frontier.kyoto-u.ac.jp