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Takeshi Sekiguchi Last modified date:2023.05.16

Assistant Professor / Molecular Biology
Department of Molecular Biology
Faculty of Medical Sciences

Graduate School

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 Reseacher Profiling Tool Kyushu University Pure
Academic Degree
Country of degree conferring institution (Overseas)
Field of Specialization
Molecular biology, Biochemstry, Cell biology, Molecular ecology
Total Priod of education and research career in the foreign country
Outline Activities
I isolated mutated genes, such as CCG1/TAF250, RCC1/RanGEF, DDX3 using temperature sensitive BHK21 cell lines.
Now, I am studying the RagA family proteins on mTORC1 regulation in mammalian cells and yeast homologue genes.
Research Interests
  • Elucidation of mechanisms of cell response against oxidative stress
    keyword : 8oxoGuanine, oxidative RNA
  • Elucidation of molecular mechanisms of cell growth and arrest in eukaryotic cells.
    keyword : cell cycle, GTP binding protein, GTR1/2、Rag A/B, Rag C/D, RCC1, Ran
    1997.04~2023.03Elucidation of molecular mechanisms of cell growth and arrest in eukaryotic cells..
  • Molecular ecology of carnivora
    keyword : species determination, sex determination, individual identification
  • Studies about the effect of fucoidan on cell.
    keyword : fucoidan
Academic Activities
1. Takeshi Sekiguchi, Takashi Ishii, Yoshiaki Kamada, Minoru Funakoshi, Hideki Kobayashi, Nobuaki Furuno, Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae, Biochemical and Biophysical Research Communications , , 598, 107-112, 2022.02, Yeast Gtr1p is a GTPase that forms a heterodimer with Gtr2p, another GTPase; it is involved in regulating TORC1 activity in nutrient signaling, including amino acid availability and growth control. Gtr1p is a positive regulator of TORC1, a kinase that regulates various cellular functions (e.g., protein synthesis and autophagy) under specific nutrient and environmental conditions, including oxidative stress. In this study, we examined the roles of Gtr1p in oxidative stress responses. We found that yeast cells expressing guanosine diphosphatase (GDP)-bound Gtr1p (Gtr1-S20Lp) were resistant to hydrogen peroxide (H2O2), whereas guanosine triphosphate (GTP)-bound Gtr1p (Gtr1-Q65Lp) was sensitive to H2O2 compared with the wild type. Consistent with these findings, yeast cells lacking Iml1p, a component of the GTPase-activating protein complex for Gtr1p, exhibited the H2O2-sensitive phenotype. In gtr1S20L cells, autophagy was highly induced under oxidative stress. gtr1Q65L cells showed decreased expression of the SNQ2 gene, which encodes a multidrug transporter involved in resistance to oxidative stress, and the overexpression of SNQ2 rescued the oxidative stress sensitivity of gtr1Q65L cells. These results suggest that Gtr1p is involved in oxidative stress responses through mechanisms that include autophagy and SNQ2 expression..
2. Takeshi Sekiguchi, Takashi Ishii, Hideki Kobayashi, Nobuaki Furuno, WDR35 is involved in subcellular localization of acetylated tubulin in293T cells, Biochemical and Biophysical Research Communications,, 547, 169-175, 2021.04, WDR35/IFT121 is an intraflagellar transport protein in primary cilia, which is associated with RagA, an
mTORC1-activating protein. To elucidate the functions of the interaction between WDR35 and RagA in
primary cilia, as well as mTOR signaling, we identified WDR35-interacting proteins using mass spectrometry.We found that WDR35 associates with CCT complex proteins including TCP1/CCT1, which act asmolecular chaperones for a-tubulin folding. Immunostaining showed that acetylated a-tubulin was
concentrated in the vicinity of primary cilia in 293T cells. In contrast, acetylated tubulin was dispersed inWDR35 partial knockout cells established from 293T cells. Similarly, scattered subcellular localization ofacetylated tubulin was observed in RagA knockout cells. RagA was present in the primary cilia of NIH3T3cells, and the GDP form of RagA exhibited strong binding to WDR35 and negative regulation of primarycilium formation. These results suggest that WDR35 is involved in the subcellular localization of acetylatedtubulin in primary cilia via its interactions with TCP1 and/or RagA family proteins..
3. Takeshi Sekiguchi, Nobuaki Furuno, Takashi Ishii, Eiji Hirose, Fumiko Sekiguchi, Yonggang Wang, and Hideki Kobayashi, RagA, an mTORC1 activator, interacts with a hedgehog signaling protein, WDR35/IFT121, Genes to Cells,, 24, 2, 151-161, 2019.02, [URL].
4. Takeshi Sekiguchi, Yoshiaki Kamada, Nobuaki Furuno, Minoru Funakoshi, Hideki Kobayashi, Amino acid residues required for Gtr1p-Gtr2p complex formation and its interactions with the Ego1p-Ego3p complex and TORC1 components in yeast, Genes to cells, 19, 6, 449-463, 2014.06, The yeast Ras-like GTPases Gtr1p and Gtr2p form a heterodimer, are implicated in the regulation of TOR complex 1 (TORC1), and play pivotal roles in cell growth. Gtr1p and Gtr2p bind Ego1p and Ego3p, which are tethered to the endosomal and vacuolar membranes where TORC1 functions are regulated through a relay of amino acid signaling interactions. The mechanisms by which Gtr1p and Gtr2p activate TORC1 remain obscure. We probed the interactions of the Gtr1p-Gtr2p complex with the Ego1p-Ego3p complex and TORC1 subunits. Mutations in the region (179-220 a.a.) following the nucleotide-binding region of Gtr1p and Gtr2p abrogated their mutual interaction and resulted in a loss in function, suggesting that complex formation between Gtr1p and Gtr2p was indispensable for TORC1 function. A modified yeast two-hybrid assay revealed that Gtr1p-Gtr2p complex formation is important for its interaction with the Ego1p-Ego3p complex. GTP-bound Gtr1p interacted with the region containing the HEAT repeats of Kog1p and the C-terminal region of Tco89p. The GTP-bound Gtr2p suppressed a Kog1p mutation. Our findings indicate that the interactions of the Gtr1p-Gtr2p complex with the Ego1p-Ego3p complex and TORC1 components Kog1p and Tco89p play a role in TORC1 function..
5. Takeshi Sekiguchi, Riyoko Itoh, Hiroshi Hayakawa, Mutsuo Sekiguchi, Elimination and utilization of oxidized Guanine nucleotides in the synthesis of RNA and its precursors., J Biol Chem. , doi: 10.1074/jbc.M112.418723. , 288, 12, 8128-8135, 2013.03.
6. Sekiguchi, T., Hayashi, N., Wang, Y., Kobayashi, H., Genetic evidence that Ras-like GTPases, Gtr1p and Gtr2p, are involved in epigenetic control of gene expression in Saccharomyces cerevisiae, Biochem Biophys Res Commun, 368, 3, 748-754, 2008.04.
7. Sekiguchi1,T., Hayano,T., Yanagida, M., Takahashi,N., Nishimoto,T., NOP132 is required for proper nucleolus localization of DEAD-box RNA helicase DDX47., Nucleic Acid Res., 34,4593-4608, 2006.09.
8. Sekiguchi, T., Iida, H., Fukumura, J. and Nishimoto T, Human DDX3Y, the Y-encoded isoform of RNA helicase DDX3, rescues a hamster temperature-sensitive ET24 mutant cell line with a DDX3X mutation., Exp. Cell. Res., 10.1016/j.yexcr.2004.07.005, 300, 1, 213-222, Vol.300 pp213-222, 2004.10.
9. Sekiguchi, T., Todaka Y., Wang YG., Hirose, E., Nakashima, N. and Nishimoto, T., A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D., J. Biol. Chem., 10.1074/jbc.M305935200, 279, 9, 8343-8350, Vol.279 pp8343-8350, 2004.01.
10. Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M. and Nishimoto, T., Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins Rag A and Rag B., J. Biol. Chem., 10.1074/jbc.M004389200, 276, 10, 7246-7257, Vol.276,No.10,pp.7246-7257, 2001.01.
11. T, Sekiguchi, T.Nishimoto and T. Hunter, Overexpression of D-type cyclins, E2F-1, SV40 large T antigen and HPV16 E7 rescue cell cycle arrest of tsBN462 cells caused by the CCG1/TAFII250 mutation, Oncogene., 10.1038/sj.onc.1202508, 18, 10, 1797-1806, Vol.18,pp.1797-1806, 1999.03.
12. Sekiguchi, T., T. Hunter, Induction of growth arrest and cell death by overexpression of the cyclin-Cdk inhibitor p21 in hamster BHK21 cells, Oncogene., Vol.16,pp.369-380, 1998.01.
13. Sekiguchi,T., Nohiro,Y., Nakamura,Y., Hisamoto,N.and T.Nishimoto., The human CCG1 gene, essential for progression of the G1 phase, encodes a 210-Kilodalton nuclear DNA-binding protein, Molecular and Cellular Biology., 11, 6, 3317-3325, Vol.11,pp.3317-3325, 1991.11.
14. Uchida,S., Sekiguchi,T., Nishitani,H., Miyauchi,K., Ohtsubo,M.and T.Nishimoto., Premature chromosome condensation is induced by a point mutation in the hamster RCC1 gene, Molecular and Cellular Biology., 10, 2, 577-584, Vol.10,pp.577-584, 1990.10.
15. Sekiguchi,T., Miyata,T.and T.Nishimoto., Molecular cloning of the cDNA of human X chromosomal gene (CCG1) which complements the temperature-sensitive G1 mutants, tsBN462 and ts13, of the BHK cell line, The EMBO Journal., 7, 6, 1683-1687, Vol.7,pp.1683-1687, 1988.01.
1. A role of S.cerevisae Gtr1p on toxic substance exclusion.
2. 関口 猛, Riyoko Itoh, Hiroshi Hayakawa, Mutsuo Sekiguchi, Elimination of oxidized nucleic acid, 第86回日本生化学会大会, 2013.09, During the de novo synthesis of guanine nucleotides, GMP is formed first, which is converted to GDP by guanylate kinase (GMK), an essential protein for E.coli. This enzyme hardly acts on an oxidized form of GMP (8-oxo-GMP), formed by the oxidation of GMP or by the cleavage of 8-oxo-GDP and 8-oxo-GTP by MutT protein. Although the formation of 8-oxo-GDP from 8-oxo-GMP is thus prevented, 8-oxo-GDP itself may be produced by the oxidation of GDP by ROS. The 8-oxo-GDP thus formed can be converted to 8-oxo-GTP, since nucleoside diphosphate kinase and adenylate kinase, both of which catalyze conversion of GDP to GTP, do not discriminate 8-oxo-GDP from normal GDP. The 8-oxo-GTP produced in this way and also by the oxidation of GTP can be used for RNA synthesis. This misincorporation is prevented by MutT protein, which has a potential to cleave 8-oxo-GTP as well as 8-oxo-GDP to 8-oxo-GMP. When 14C-labeled 8-oxo-GTP was applied to CaCl2-permeabilized cells of mutT- mutant strain, it could be incorporated into RNA at 4% of the rate for GTP. Escherichia coli cells appear to possess mechanisms to prevent misincorporation of 8-oxo-Gua into RNA..
3. Analysis of fate of guanine nucleotide exogenously introduced into HeLa cells..
4. Interaction between Gtr1-Gtr2 and components of Tor complex1.
5. Analysis of Gtr1-Gtr2 complex on TOR signal transduction pathway..
6. Characterization of Gtr1/2 small G proteins..
7. Protein phosphorylation of RCC1, a RanGEF.
8. A study on the possible function of S23N GTR2 (GDP form).
Membership in Academic Society
  • The Genetics Society of Japan
  • The Mammalogical Society of Japan
  • Japanese cancer association
  • The molecular biology society of Japan
Educational Activities
KIKAN education in Ito campus.
Professional and Outreach Activities
2007,March, Present my research for JST-Kyushu University joint seeds meeting in Tokyo..