| [Degree] | PhD | |
| [Academic Society] | The Zoological Society of Japan, The Molecular Biology Society of Japan, The Japanese Biochemical Society |
| [Research Subjects] | oocyte maturation, ovulation, proteasome, cyclin, membrane progestin receptor | |
| [Publications] |
[1] Toshinobu Tokumoto, Masakane Yamashita, Mika Tokumoto, Yoshinao Katsu, Ryo Horiguchi, Hiroko Kajiura, Yoshitaka Nagahama (1997) Initiation of cyclin B degradation by the 26S proteasome upon egg activation. J. Cell Biol., 138, 1313-1322. [2] Toshinobu Tokumoto, Mika Tokumoto, Keiji Seto, Ryo Horiguchi, Yoshitaka Nagahama, Shinpei Yamada, Katsutoshi Ishikawa, Manfred J. Lohka (1999) Disappearance of a novel protein component of the 26S proteasome during Xenopus oocyte maturation. Exp. Cell Res., 247, 313-319. [3] Toshinobu Tokumoto, Mika Tokumoto, Ryo Horiguchi, Katsutoshi Ishikawa, Yoshitaka Nagahama (2004). Diethylstilbestrol induces fish oocyte maturation. PNAS, USA, 101, 3686-3690. [4] Ryo Horiguchi, Michiyasu Yoshikuni, Mika Tokumoto, Yoshitaka Nagahama Toshinobu Tokumoto (2005) Identification of a protein kinase which phosphorylates a subunit of the 26S proteasome and changes in its activity during meiotic cell cycle in goldfish oocytes. Cell. Sig., 17, 205-215. [5] Ryo Horiguchi, Hideo Dohra, Toshinobu Tokumoto (2006) Comparative proteome analysis of changes in the 26S proteasome during oocyte maturation in goldfish. Proteomics, 14, 4195-4202. |
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| [E-mail] | sbttoku |
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| [Others] |
Link to Tokumoto laboratory Research subjects 1. Role of proteasomes in the regulation of meiotic cell cycle: The proteasomes are large, multi-subunit particles that act as the proteolytic machinery for most of the regulated intracellular protein degradation in eukaryotic cells. An alteration in proteasome function may be important for the regulation of meiotic cell cycle. We suggest that the N-terminal restricted cleavage of cyclin B by 26S proteasome allows cyclin to be ubiquitinated. We further demonstrated that the 26S proteasome purified from immature oocytes can digest cyclin B, but the 26S proteasome purified from mature oocytes cannot. From these results, it is revealed that particular activity of the 26S proteasome differ between these purified fractions. Then, we started the analysis of differences in components in these fractions. In recent proteomic analysis, we identified changes in spotting pattern of four proteasomal subunits and four proteasome interacting proteins. These results demonstrated that modifications of proteasomal subunits and proteins interacting with proteasomes are conducted during oocyte maturation in goldfish and suggest that these modifications are implicated in the regulation of oocyte maturation. Then our current interest is identification of the modifications to proteasomal subunits and interacting proteins that is critical for regulation of proteasome activity. 2. Regulation and function of membrane progestin receptor: The induction of oocyte maturation by progestins in fish and amphibians is arguably the most thoroughly investigated and best understood mechanisms of nongenomic steroid actions mediated through activation of receptors on the cell surface. Fully grown fish oocytes are arrested at prophase of the first meiotic division prior to oocyte maturation. A surge in gonadotropin secretion induces the final phase of oocyte maturation, including germinal vesicle breakdown, indirectly by inducing the synthesis of maturation inducing steroids or substances (MIS) by the ovarian follicles. The MISs bind to specific progestin receptors on the oocyte plasma membrane to trigger a cascade of intracellular second messengers including de novo synthesis of cyclin B protein leading to activation of M-phase promoting factor. Recently, a novel cDNA, named mPR, was identified that encodes a protein with the characteristics of the membrane progestin receptor mediating the MIS induction of oocyte maturation. The induction of oocyte maturation in fish by progestins has previously been shown to be a valuable model for investigating interference of nongenomic steroid actions by endocrine-disrupting chemicals (EDCs). For example, we found that treatment of goldfish and zebrafish oocytes with an endocrine disrupting chemical (EDC), diethylstilbestrol (DES), alone induces oocyte maturation. Our current research is developed to study the structure of mPR in vivo and the mechanisms how to mediate the signals of MIS or EDCs into oocytes. |
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