Updated on 2026/03/18

写真a

 
SHIMASAKI Takafumi
 
Organization
Graduate School of Pharmaceutical Sciences Department of Basic Medicinal Sciences Assistant Professor
Graduate School
Graduate School of Pharmaceutical Sciences
Undergraduate School
School of Agricultural Sciences Department of Applied Biosciences
Title
Assistant Professor
Contact information
メールアドレス

Degree 1

  1. 博士(創薬科学) ( 2017.3   名古屋大学 ) 

Research History 1

  1. Nagoya University   School of Agricultural Sciences

    2018.4

Professional Memberships 4

  1. 酵母遺伝学フォーラム

  2. 日本ゲノム微生物学会

  3. 日本分子生物学会

  4. 日本農芸化学会

Committee Memberships 1

  1. 日本農芸化学会中部支部   会計幹事  

    2021.3 - 2023.2   

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    Committee type:Academic society

 

Papers 28

  1. Responses to nutrient starvation in the fission yeast Schizosaccharomyces pombe Reviewed Open Access

    Ohtsuka, H; Shimasaki, T; Aiba, H

    MICROBIOLOGICAL RESEARCH   Vol. 303   page: 128387   2026.2

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    Language:English   Publisher:Microbiological Research  

    In nature, nutrient-poor environments are more common than exposure to nutrient-rich environments, and living organisms have developed countermeasures to survive nutrient starvation. Increasing research has revealed beneficial aspects of starvation for an individual’s life, including lifespan extension. The fission yeast Schizosaccharomyces pombe is a model unicellular eukaryotic organism and has greatly contributed to the understanding of various cellular processes, including the cell cycle, cell morphology, sexual development, cell lifespan, and nutritional responses. Traditionally, research on starvation in fission yeast has focused on glucose starvation and nitrogen starvation. Recently, studies on cellular responses to the starvation of various nutrients, such as phosphorus, sulfur, iron, zinc, copper, and amino acids have been reported, revealing similarities and differences among the various types of nutrient starvation. In fission yeast, Ecl proteins, which are conserved among fungi, can sense the starvation of multiple nutrients. These proteins also repress the target of rapamycin complex 1 (TORC1), which is conserved across eukaryotes. They channel a variety of starvation signals into common cellular responses, such as growth arrest, sexual differentiation, autophagy, and lifespan extension. This review summarizes and discusses the signaling mechanisms involved in the initial cellular responses of fission yeast to the starvation of various nutrients.

    DOI: 10.1016/j.micres.2025.128387

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  2. Characterization of P-type H<SUP>+</SUP>-ATPase Pma1 inhibitors that extend chronological lifespan in fission yeast Reviewed Open Access

    Tamura, M; Yamashita, W; Hibi, T; Inui, S; Tanaka, K; Ozako, M; Shimasaki, T; Ohtsuka, H; Shibuya, M; Yamamoto, Y; Yokoshima, S; Aiba, H

    MOLECULAR GENETICS AND GENOMICS   Vol. 300 ( 1 ) page: 58   2025.6

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    Language:English   Publisher:Molecular Genetics and Genomics  

    Inhibition of the activity of Pma1, a widely conserved P-type proton exporting ATPase, has been shown to extend the chronological lifespan (CLS) in fission yeast Schizosaccharomyces pombe. To develop a specific inhibitor for Pma1 of S. pombe, we focused on Si01, a candidate inhibitor of Saccharomyces cerevisiae Pma1. First, we have established a method for synthesis of Si01 and then investigated its Pma1 inhibitory activity and lifespan extension effect in fission yeast. Second, we also synthesized derivatives of Si01 and determined the minimum structure required for inhibition of S. pombe Pma1. Here we showed that the inhibitory activity of Pma1 correlates with the effect of lifespan extension. Si01 reduced the activity of purified Pma1 protein and extended the CLS of not only fission yeast but also budding yeast. These results provide a molecular basis for understanding the mechanism of Pma1 inhibition and the potential for developing molecules that regulate lifespan.

    DOI: 10.1007/s00438-025-02264-4

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  3. Novel TORC1 inhibitor Ecl1 is regulated by phosphorylation in fission yeast Reviewed Open Access

    Ohtsuka, H; Kawai, S; Ito, Y; Kato, Y; Shimasaki, T; Imada, K; Otsubo, Y; Yamashita, A; Mishiro-Sato, E; Kuwata, K; Aiba, H

    AGING CELL   Vol. 24 ( 4 ) page: e14450   2025.4

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    Language:English   Publisher:Aging Cell  

    Extender of chronological lifespan 1 (Ecl1) inhibits target of rapamycin complex 1 (TORC1) and is necessary for appropriate cellular responses to various stressors, such as starvation, in fission yeast. However, little is known about the effect of posttranslational modifications on Ecl1 regulation. Thus, we investigated the phosphorylation levels of Ecl1 extracted from yeast under conditions of sulfur or metal starvation. Mass spectrometry analysis revealed that Ecl1 was phosphorylated at Thr7, and the level was decreased by starvation. The phosphorylation-mimetic mutation of Thr7 significantly reduced the effects of Ecl1-induced cellular responses to starvation, suggesting that Ecl1 function was suppressed by Thr7 phosphorylation. By contrast, regardless of starvation exposure, TORC1 was significantly suppressed, even when Thr7 phosphorylation-mimetic Ecl1 was overexpressed. This indicated that Ecl1 suppressed TORC1 regardless of Thr7 phosphorylation. We newly identified that Ecl1 physically interacted with TORC1 subunit RAPTOR (Mip1). Based on these evidences, we propose that, Ecl1 has dual functional modes: quantity-dependent TORC1 inhibition and Thr7 phosphorylation–dependent control of cellular function.

    DOI: 10.1111/acel.14450

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  4. Identification of <i>plb1</i> mutation that extends longevity via activating Sty1 MAPK in <i>Schizosaccharomyces pombe</i> Reviewed Open Access

    Maekawa, Y; Matsui, K; Okamoto, K; Shimasaki, T; Ohtsuka, H; Tani, M; Ihara, K; Aiba, H

    MOLECULAR GENETICS AND GENOMICS   Vol. 299 ( 1 ) page: 20   2024.12

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    Language:English   Publisher:Molecular Genetics and Genomics  

    To understand the lifespan of higher organisms, including humans, it is important to understand lifespan at the cellular level as a prerequisite. So, fission yeast is a good model organism for the study of lifespan. To identify the novel factors involved in longevity, we are conducting a large-scale screening of long-lived mutant strains that extend chronological lifespan (cell survival in the stationary phase) using fission yeast. One of the newly acquired long-lived mutant strains (No.98 mutant) was selected for analysis and found that the long-lived phenotype was due to a missense mutation (92Phe → Ile) in the plb1<sup>+</sup> gene. plb1<sup>+</sup> gene in fission yeast is a nonessential gene encoding a homolog of phospholipase B, but its functions under normal growth conditions, as well as phospholipase B activity, remain unresolved. Our analysis of the No.98 mutant revealed that the plb1 mutation reduces the integrity of the cellular membrane and cell wall and activates Sty1 via phosphorylation.

    DOI: 10.1007/s00438-024-02107-8

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  5. A novel transcription factor Sdr1 involving sulfur depletion response in fission yeast Reviewed Open Access

    Ohtsuka, H; Ohara, K; Shimasaki, T; Hatta, Y; Maekawa, Y; Aiba, H

    GENES TO CELLS   Vol. 29 ( 8 ) page: 667 - 680   2024.8

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    In the fission yeast Schizosaccharomyces pombe, the response to sulfur depletion has been less studied compared to the response to nitrogen depletion. Our study reveals that the fission yeast gene, SPCC417.09c, plays a significant role in the sulfur depletion response. This gene encodes a protein with a Zn<inf>2</inf>Cys<inf>6</inf> fungal-type DNA-binding domain and a transcription factor domain, and we have named it sdr1<sup>+</sup> (sulfur depletion response 1). Interestingly, while sulfur depletion typically induces autophagy akin to nitrogen depletion, we found that autophagy was not induced under sulfur depletion in the absence of sdr1<sup>+</sup>. This suggests that sdr1<sup>+</sup> is necessary for the induction of autophagy under conditions of sulfur depletion. Although sdr1<sup>+</sup> is not essential for the growth of fission yeast, its overexpression, driven by the nmt1 promoter, inhibits growth. This implies that Sdr1 may possess cell growth-inhibitory capabilities. In addition, our analysis of Δsdr1 cells revealed that sdr1<sup>+</sup> also plays a role in regulating the expression of genes associated with the phosphate depletion response. In conclusion, our study introduces Sdr1 as a novel transcription factor that contributes to an appropriate cellular nutrient starvation response. It does so by inhibiting inappropriate cell growth and inducing autophagy in response to sulfur depletion.

    DOI: 10.1111/gtc.13136

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  6. Low-Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, <i>Saccharomyces cerevisiae</i>, and <i>Schizosaccharomyces pombe</i> Reviewed Open Access

    Ohtsuka, H; Shimasaki, T; Aiba, H

    ADVANCED BIOLOGY   Vol. 8 ( 5 ) page: e2400138   2024.5

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    Language:English   Publisher:Advanced Biology  

    Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low-molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low-molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low-molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.

    DOI: 10.1002/adbi.202400138

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  7. <i>ecl</i> family genes: Factors linking starvation and lifespan extension in <i>Schizosaccharomyces pombe</i> Open Access

    Ohtsuka, H; Otsubo, Y; Shimasaki, T; Yamashita, A; Aiba, H

    MOLECULAR MICROBIOLOGY   Vol. 120 ( 5 ) page: 645 - 657   2023.11

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    In the fission yeast Schizosaccharomyces pombe, the duration of survival in the stationary phase, termed the chronological lifespan (CLS), is affected by various environmental factors and the corresponding gene activities. The ecl family genes were identified in the genomic region encoding non-coding RNA as positive regulators of CLS in S. pombe, and subsequently shown to encode relatively short proteins. Several studies revealed that ecl family genes respond to various nutritional starvation conditions via different mechanisms, and they are additionally involved in stress resistance, autophagy, sexual differentiation, and cell cycle control. Recent studies reported that Ecl family proteins strongly suppress target of rapamycin complex 1, which is a conserved eukaryotic nutrient-sensing kinase complex that also regulates longevity in a variety of organisms. In this review, we introduce the regulatory mechanisms of Ecl family proteins and discuss their emerging findings.

    DOI: 10.1111/mmi.15134

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  8. The ecl family gene ecl3<SUP>+</SUP> is induced by phosphate starvation and contributes to sexual differentiation in fission yeast Reviewed Open Access

    Ohtsuka, H; Sakata, H; Kitazaki, Y; Tada, M; Shimasaki, T; Otsubo, Y; Maekawa, Y; Kobayashi, M; Imada, K; Yamashita, A; Aiba, H

    JOURNAL OF CELL SCIENCE   Vol. 136 ( 6 )   2023.3

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    In Schizosaccharomyces pombe, ecl family genes are induced by several signals, such as starvation of various nutrients, including sulfur, amino acids and Mg<sup>2+</sup>, and environmental stress, including heat or oxidative stress. These genes mediate appropriate cellular responses and contribute to the maintenance of cell viability and induction of sexual differentiation. Although this yeast has three ecl family genes with overlapping functions, any environmental conditions that induce ecl3<sup>+</sup> remain unidentified. We demonstrate that ecl3<sup>+</sup> is induced by phosphate starvation, similar to its chromosomally neighboring genes, pho1<sup>+</sup> and pho84<sup>+</sup>, which respectively encode an extracellular acid phosphatase and an inorganic phosphate transporter. ecl3<sup>+</sup> expression was induced by the transcription factor Pho7 and affected by the cyclin-dependent kinase (CDK)-activating kinase Csk1. Phosphate starvation induced G1 arrest and sexual differentiation via ecl family genes. Biochemical analyses suggested that this G1 arrest was mediated by the stabilization of the CDK inhibitor Rum1, which was dependent on ecl family genes. This study shows that ecl family genes are required for appropriate responses to phosphate starvation and provides novel insights into the diversity and similarity of starvation responses.

    DOI: 10.1242/jcs.260759

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  9. <i>Metarhizium robertsii </i>COH1 functionally complements <i>Schizosaccharomyces pombe</i> Ecl family proteins Open Access

    Ohtsuka Hokuto, Kawai Sawa, Otsubo Yoko, Shimasaki Takafumi, Yamashita Akira, Aiba Hirofumi

    The Journal of General and Applied Microbiology   Vol. 69 ( 6 ) page: 335 - 338   2023

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    Language:English   Publisher:Applied Microbiology, Molecular and Cellular Biosciences Research Foundation  

    <p>The fission yeast <i>Schizosaccharomyces pombe ecl</i> family genes respond to various starvation signals and induce appropriate intracellular responses, including the extension of chronological lifespan and induction of sexual differentiation. Herein, we propose that the colonization of hemocoel 1 (COH1) protein of <i>Metarhizium robertsii</i>, an insect-pathogenic fungus, is a functional homolog of <i>S. pombe</i> Ecl1 family proteins.</p>

    DOI: 10.2323/jgam.2023.09.001

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  10. Sporulation: A response to starvation in the fission yeast <i>Schizosaccharomyces pombe</i> Reviewed Open Access

    Ohtsuka, H; Imada, K; Shimasaki, T; Aiba, H

    MICROBIOLOGYOPEN   Vol. 11 ( 3 ) page: e1303   2022.6

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    The fission yeast Schizosaccharomyces pombe employs two main strategies to adapt to the environment and survive when starved for nutrients. The strategies employ sporulation via sexual differentiation and extension of the chronological lifespan. When a cell is exposed to nutrient starvation in the presence of a cell of the opposite sex, the cells undergo fusion through conjugation and sporulation through meiosis. S. pombe spores are highly resistant to diverse stresses and may survive for a very long time. In this minireview, among the various sexual differentiation processes induced by starvation, we focused on and summarized the findings of the molecular mechanisms of spore formation in fission yeast. Furthermore, comparative measurements of the chronological lifespan of stationary phase cells and G<inf>0</inf> cells and the survival period of spore cells revealed that the spore cells survived for a long period, indicating the presence of an effective mechanism for survival. Currently, many molecules involved in sporulation and their functions are being discovered; however, our understanding of these is not complete. Further understanding of spores may not only deepen our comprehension of sexual differentiation but may also provide hints for sustaining life.

    DOI: 10.1002/mbo3.1303

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  11. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast Reviewed Open Access

    Ohtsuka, H; Matsumoto, T; Mochida, T; Shimasaki, T; Shibuya, M; Yamamoto, Y; Aiba, H

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   Vol. 86 ( 6 ) page: 775 - 779   2022.5

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    Language:English   Publisher:Bioscience Biotechnology and Biochemistry  

    Tschimganine inhibits growth and extends the chronological lifespan in Schizosaccharomyces pombe. We synthesized a Tschimganine analog, Mochimganine, which extends the lifespan similar to Tschimganine but exhibits a significantly weaker growth inhibition effect. Based on the comparative analysis of these compounds, we propose that Tschimganine has at least 2 targets: one extends the lifespan and the other inhibits growth.

    DOI: 10.1093/bbb/zbac051

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  12. Response to leucine in Schizosaccharomyces pombe (fission yeast). Reviewed Open Access

    Ohtsuka H, Shimasaki T, Aiba H

    FEMS yeast research   Vol. 22 ( 1 )   2022.4

  13. Characterization of hexose transporter genes in the views of the chronological life span and glucose uptake in fission yeast Open Access

    Maruyama Teppei, Hayashi Kanako, Matsui Kotaro, Maekawa Yasukichi, Shimasaki Takafumi, Ohtsuka Hokuto, Shigeaki Saitoh, Aiba Hirofumi

    The Journal of General and Applied Microbiology   Vol. 68 ( 6 ) page: 270 - 277   2022

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    <p>Fission yeast, <i>Schizosaccharomyces pombe</i>, possesses eight hexose transporters, Ght1~8. In order to clarify the role of each hexose transporter on glucose uptake, a glucose uptake assay system was established and the actual glucose uptake activity of each hexose transporter-deletion mutant was measured. Under normal growth condition containing 2% glucose, ∆<i>ght5</i> and ∆<i>ght2</i> mutants showed large and small decrease in glucose uptake activity, respectively.<b> </b>On the other hand, the other deletion mutants did not show any decrease in glucose uptake activity indicating that, in the presence of Ght5 and Ght2, the other hexose transporters do not play a significant role in glucose uptake. To understand the relevance between glucose uptake and lifespan regulation, we measured the chronological lifespan of each hexose transporter deletion mutant, and found that only ∆<i>ght5</i> mutant showed a significant lifespan extension. Based on these results we showed that Ght5 is mainly involved in the glucose uptake in <i>Schizosaccharomyces pombe</i>, and suggested that the ∆<i>ght5</i> mutant has prolonged lifespan due to physiological changes similar to calorie restriction.</p>

    DOI: 10.2323/jgam.2022.05.006

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  14. Identification of ksg1 mutation showing long-lived phenotype in fission yeast Reviewed Open Access

    Matsui Kotaro, Okamoto Keisuke, Hasegawa Tomoka, Ohtsuka Hokuto, Shimasaki Takafumi, Ihara Kunio, Goto Yuhei, Aoki Kazuhiro, Aiba Hirofumi

    GENES TO CELLS   Vol. 26 ( 12 ) page: 967 - 978   2021.12

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    DOI: 10.1111/gtc.12897

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  15. Response to sulfur in Schizosaccharomyces pombe Reviewed Open Access

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    FEMS YEAST RESEARCH   Vol. 21 ( 5 )   2021.8

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    DOI: 10.1093/femsyr/foab041

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  16. Extension of chronological lifespan in Schizosaccharomyces pombe Reviewed Open Access

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    GENES TO CELLS   Vol. 26 ( 7 ) page: 459 - 473   2021.7

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    DOI: 10.1111/gtc.12854

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  17. Identification of sur2 mutation affecting the lifespan of fission yeast Reviewed Open Access

    Kurauchi Tatsuhiro, Matsui Kotaro, Shimasaki Takafumi, Ohtsuka Hokuto, Tsubouchi Satoshi, Ihara Kunio, Tani Motohiro, Aiba Hirofumi

    FEMS MICROBIOLOGY LETTERS   Vol. 368 ( 12 )   2021.6

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    DOI: 10.1093/femsle/fnab070

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  18. Genes affecting the extension of chronological lifespan in Schizosaccharomyces pombe (fission yeast) Reviewed Open Access

    Ohtsuka Hokuto, Shimasaki Takafumi, Aiba Hirofumi

    MOLECULAR MICROBIOLOGY   Vol. 115 ( 4 ) page: 623 - 642   2021.4

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    DOI: 10.1111/mmi.14627

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  19. Magnesium depletion extends fission yeast lifespan via general amino acid control activation Reviewed Open Access

    Ohtsuka, H; Kobayashi, M; Shimasaki, T; Sato, T; Akanuma, G; Kitaura, Y; Otsubo, Y; Yamashita, A; Aiba, H

    MICROBIOLOGYOPEN   Vol. 10 ( 2 ) page: e1176   2021.3

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    Nutrients including glucose, nitrogen, sulfur, zinc, and iron are involved in the regulation of chronological lifespan (CLS) of yeast, which serves as a model of the lifespan of differentiated cells of higher organisms. Herein, we show that magnesium (Mg<sup>2+</sup>) depletion extends CLS of the fission yeast Schizosaccharomyces pombe through a mechanism involving the Ecl1 gene family. We discovered that ecl1<sup>+</sup> expression, which extends CLS, responds to Mg<sup>2+</sup> depletion. Therefore, we investigated the underlying intracellular responses. In amino acid auxotrophic strains, Mg<sup>2+</sup> depletion robustly induces ecl1<sup>+</sup> expression through the activation of the general amino acid control (GAAC) pathway—the equivalent of the amino acid response of mammals. Polysome analysis indicated that the expression of Ecl1 family genes was required for regulating ribosome amount when cells were starved, suggesting that Ecl1 family gene products control the abundance of ribosomes, which contributes to longevity through the activation of the evolutionarily conserved GAAC pathway. The present study extends our understanding of the cellular response to Mg<sup>2+</sup> depletion and its influence on the mechanism controlling longevity.

    DOI: 10.1002/mbo3.1176

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  20. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast Reviewed Open Access

    Ohtsuka H*, Matsumoto T*, Mochida T, Shimasaki T, Shibuya M, Yamamoto Aiba H

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY     2021

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    DOI: 10.1093/bbb/zbac051

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  21. Cdc13 (cyclin B) is degraded by autophagy under sulfur depletion in fission yeast Reviewed

    Ohtsuka H, Hatta Y, Hayashi K, Shimasaki T, Otsubo Y, Ito Y, Tsutsui Y, Hattori N, Yamashita A, Murakami H, Aiba H.

    Autophagy Reports     2021

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    DOI: 10.1080/27694127.2022.2047442

  22. Sulfur depletion induces autophagy through Ecl1 family genes in fission yeast Reviewed Open Access

    Shimasaki, T; Okamoto, K; Ohtsuka, H; Aiba, H

    GENES TO CELLS   Vol. 25 ( 12 ) page: 825 - 830   2020.12

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    Autophagy is an intracellular degradation system widely conserved among various species. Autophagy is induced by the depletion of various nutrients, and this degradation mechanism is essential for adaptation to such conditions. In this study, we demonstrated that sulfur depletion induces autophagy in the fission yeast Schizosaccharomyces pombe. Based on the finding that autophagy induced by sulfur depletion was completely abolished in a mutant in which the ecl1, ecl2 and ecl3 genes were deleted (Δecls), we report that these three genes are essential for the induction of autophagy by sulfur depletion. Furthermore, autophagy-defective mutant cells exhibited poor growth and short lifespan (compared with wild-type cells) under the sulfur-depleted condition. These results indicated that the mechanism of autophagy is necessary for the appropriate adaptation to sulfur depletion.

    DOI: 10.1111/gtc.12815

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  23. gas1 mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in Schizosaccharomyces pombe Reviewed Open Access

    Imai Yuki, Shimasaki Takafumi, Enokimura Chihiro, Ohtsuka Hokuto, Tsubouchi Satoshi, Ihara Kunio, Aiba Hirofumi

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   Vol. 84 ( 2 ) page: 330 - 337   2020.2

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    DOI: 10.1080/09168451.2019.1676695

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  24. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1 Reviewed

    Ohtsuka Hokuto, Kato Takanori, Sato Teppei, Shimasaki Takafumi, Kojima Takaaki, Aiba Hirofumi

    MOLECULAR GENETICS AND GENOMICS   Vol. 294 ( 6 ) page: 1499 - 1509   2019.12

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    DOI: 10.1007/s00438-019-01592-6

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  25. Tschimganine and its derivatives extend the chronological life span of yeast via activation of the Sty1 pathway Reviewed Open Access

    Hibi Takahide, Ohtsuka Hokuto, Shimasaki Takafumi, Inui Shougo, Shibuya Masatoshi, Tatsukawa Hideki, Kanie Kei, Yamamoto Yoshihiko, Aiba Hirofumi

    GENES TO CELLS   Vol. 23 ( 8 ) page: 620 - 637   2018.8

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    DOI: 10.1111/gtc.12604

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  26. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome Reviewed Open Access

    Ohtsuka Hokuto, Takinami Masahiro, Shimasaki Takafumi, Hibi Takahide, Murakami Hiroshi, Aiba Hirofumi

    MOLECULAR MICROBIOLOGY   Vol. 105 ( 1 ) page: 84 - 97   2017.7

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    DOI: 10.1111/mmi.13686

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  27. Ecl1 is a zinc-binding protein involved in the zinc-limitation-dependent extension of chronological life span in fission yeast Reviewed Open Access

    Shimasaki Takafumi, Ohtsuka Hokuto, Naito Chikako, Azuma Kenko, Tenno Takeshi, Hiroaki Hidekazu, Murakami Hiroshi, Aiba Hirofumi

    MOLECULAR GENETICS AND GENOMICS   Vol. 292 ( 2 ) page: 475 - 481   2017.4

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1007/s00438-016-1285-x

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  28. Ecl1 is activated by the transcription factor Atf1 in response to H2O2 stress in Schizosaccharomyces pombe Reviewed

        2014.4

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Presentations 18

  1. 分裂酵母における(Ecl1ファミリー遺伝子を介した)硫黄枯渇による細胞小型化の解析

    八田佳子, 筒井優, 服部允赳, 島崎崇史, 大塚北斗, 饗場浩文

    第42回 日本分子生物学会年会  

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    Event date: 2020.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:福岡   Country:Japan  

  2. Mg枯渇時における分裂酵母の経時寿命延長因子Ecl1 Family遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    日本農芸化学会中部支部第187回例会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  3. 分裂酵母におけるGhtファミリータンパク質の欠失がグルコース取り込みと寿命へ与える影響の解析

    丸山哲平、林可奈子、島崎嵩史、大塚北斗、齋藤成昭、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  4. 分裂酵母におけるTschimganineの作用機構の解析

    松本拓磨、大塚北斗、持田尚宏、島崎嵩史、澁谷正俊、山本芳彦、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  5. 分裂酵母における硫黄枯渇制限下での細胞小型化の解析

    八田佳子、筒井優、服部允赳、島崎嵩史、大塚北斗、饗場浩文

    日本農芸化学会中部支部第187回例会 

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    Event date: 2020.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  6. 分裂酵母において硫黄枯渇はEcl1ファミリー遺伝子依存的にオートファジーを誘導する

    島崎嵩史, 岡本啓佑, 大塚北斗, 饗場浩文

    酵母遺伝学フォーラム第53回研究報告会 

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    Event date: 2020.9

    Presentation type:Oral presentation (general)  

    Venue:Web開催   Country:Japan  

  7. 分裂酵母におけるTschimganineの作用機構の解析

    松本拓磨、大塚北斗、持田尚宏、島崎嵩史、山本芳彦、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  8. 経時寿命が延長する分裂酵母変異株のスクリーニングと新規寿命関連因子の同定

    松井滉太朗、岡本啓佑、長谷川朋香、島崎嵩史、大塚北斗、井原邦夫、後藤祐平、青木一洋、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  9. Mg枯渇時における分裂酵母の経時寿命延長因子Ecl1ファミリー遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  10. 分裂酵母における硫黄枯渇による細胞小型化の解析

    八田佳子、筒井優、服部允赳、大塚北斗、島崎嵩史、饗場浩文

    酵母遺伝学フォーラム第53回研究報告会  

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    Event date: 2020.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:Web開催   Country:Japan  

  11. 分裂酵母におけるアミノ酸枯渇応答機構の解析

    島崎嵩史、大塚北斗、佐藤哲平、赤沼元気、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:名古屋   Country:Japan  

  12. 経時寿命が延長する分裂酵母変異株のスクリーニングと新規寿命関連因子の同定

    松井滉太朗、岡本啓佑、長谷川朋香、島崎嵩史、大塚北斗、井原邦夫、中村彰伸、後藤祐平、青木一洋、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  13. 分裂酵母における硫黄枯渇と細胞応答

    筒井優、服部允赳、八田佳子、大塚北斗、島崎嵩史、饗場浩文

    第14回 日本ゲノム微生物学会年会 

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  14. 分裂酵母におけるTschimganineの作用機構の解析

    持田尚宏、大塚北斗、松本拓磨、島崎嵩史、澁谷正俊、山本芳彦、饗場浩文

    第14回 日本ゲノム微生物学会年会  

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    Event date: 2020.3

    Language:Japanese   Presentation type:Poster presentation  

    Venue:名古屋   Country:Japan  

  15. マグネシウム枯渇条件下における分裂酵母の経時寿命延長因子Ecl1 family遺伝子の解析

    小林未来登, 佐藤哲平, 大塚北斗, 島崎嵩史, 饗場浩文

    第42回 日本分子生物学会年会  

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    Event date: 2019.12

    Language:Japanese   Presentation type:Poster presentation  

    Venue:福岡   Country:Japan  

  16. アミノ酸枯渇に応答する分裂酵母の経時寿命延長因子Ecl1 Family 遺伝子の解析

    佐藤哲平、大塚北斗、加藤敬典、島崎嵩史、饗場浩文

    酵母遺伝学フォーラム第52回研究報告会  

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    Event date: 2019.9

    Language:Japanese   Presentation type:Poster presentation  

    Venue:静岡市清水文化会館マリナート  

  17. 分裂酵母におけるgas1 変異による寿命延長機構の解析

    島崎嵩史、今井優希、榎村千尋、大塚北斗、井原邦夫、饗場浩文

    酵母遺伝学フォーラム第52回研究報告会 

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    Event date: 2019.9

    Language:Japanese   Presentation type:Oral presentation (general)  

    Venue:静岡市清水文化会館マリナート   Country:Japan  

  18. Leucine depletion extends the lifespans of fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. International conference

    Hirofumi Aiba, Hokuto Ohtsuka, Takanori Kato, Teppei Sato, and Takafumi Shimasaki

    The 10 th International Fission Yeast Meeting  

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    Event date: 2019.7

    Language:English   Presentation type:Poster presentation  

    Venue:Barcelona, Spain   Country:Spain  

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KAKENHI (Grants-in-Aid for Scientific Research) 3

  1. 酵母の生育に必須な新規キナーゼによる寿命制御機構の解明

    Grant number:25K08878  2025.4 - 2028.3

    科学研究費助成事業  基盤研究(C)

    島崎 嵩史

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    Authorship:Principal investigator 

    Grant amount:\4420000 ( Direct Cost: \3400000 、 Indirect Cost:\1020000 )

    本研究では、分裂酵母において新たに同定された寿命制御因子であるNnk1の生理学的機能の解明を行う。これまでの解析の結果から、Nnk1タンパク質が寿命制御だけでなく細胞の生育そのものに関与することが示唆されている。本研究では、Nnk1タンパク質のリン酸化基質の同定と、Nnk1タンパク質の下流で機能する因子の探索という大きく2つの解析からNnk1タンパク質の生理学的機能を明らかにし、Nnk1タンパク質による寿命制御および細胞分裂の制御メカニズムの解明を目指す。

  2. 細胞周期制御に関わる新規寿命関連因子の機能解明

    Grant number:23K13868  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  若手研究

    島崎 嵩史

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    過去に新規寿命制御因子の同定を目的として長寿命変異株のスクリーニングが行われ、解析の対象であるnnk1変異株が取得された。全ゲノムシークエンス解析の結果、機能未知の遺伝子nnk1+において変異(nnk1-35変異)が確認され、この変異が長寿命の表現型の原因であることが明らかとなった。nnk1+遺伝子は生育に必須であり、nnk1変異株も高温感受性の表現型を示すが、解析の結果、Nnk1タンパク質が寿命制御だけでなく細胞周期の制御に関与することが示唆された。本研究ではこのNnk1タンパク質の生理学的機能を明らかにし、Nnk1タンパク質による寿命制御および細胞周期制御メカニズムの解明を目指す。
    本研究では分裂酵母の寿命制御因子であるNnk1タンパク質の機能解析を行なった。Nnk1はキナーゼであるがその基質は未だに同定されていないため、N末端側にGSTタグを付加したNnk1全長タンパク質の過剰発現プラスミドを作製した。このプラスミドを酵母細胞に導入し発現誘導を行なったが、予想に反してNnk1タンパク質の過剰発現が見られなかった。この原因について調べたところ、Nnk1タンパク質のN末端側の配列が分解シグナルとなり過剰発現が抑制されていることが明らかになった。この結果を受けて、Nnk1タンパク質のC末端側のみのプラスミドを作製し発現を試みたところ、問題なく過剰発現することに成功した。また表現型の解析から、Nnk1タンパク質はこのC末端側の配列のみでもキナーゼとしての活性を十分に保持することが確認されている。現在はこの過剰発現プラスミドを用いて、リン酸化プロテオミクス解析やNnk1タンパク質と相互作用する因子の探索を行なっている。またNnk1タンパク質は生育に必須であり、nnk1-35変異株は高温条件において生育不全(TS)の表現型を示すことがこれまでの解析によって明らかになっている。そこで、高温条件においてこのTSの表現型を相補する変異株のスクリーニングを実施したところ、nnk1-35変異を保持した上で高温条件で生育可能な株を複数取得することに成功した。現在、これらの株の全ゲノムシーケンス解析を行なっており、Nnk1タンパク質の機能と関連する因子の特定を目指している。
    従来の予定通り、GSTタグを付加したNnk1全長タンパク質の発現プラスミドを作製し過剰発現を試みたところ、期待に反して過剰発現が起こらないことが判明した。この原因を特定するために解析を行なったところ、Nnk1のN末端側の配列が何らかの分解シグナルになっているようで、Nnk1タンパク質のC末端側の配列のみでプラスミドを作製し直したところ、十分に過剰発現することに成功した。なお、今回作製したNnk1のC末端側のみの配列で、Nnk1タンパク質のキナーゼとしての機能は保持されていることも確認済みである。以上のように、既に問題点の特定と解消は終えているが、この点について時間を要したため解析が予定よりもやや遅れることとなった。
    今後は、作製したNnk1-C末端の発現プラスミドを用いて、過剰発現した際のリン酸化プロテオミクス解析やプルダウンアッセイによる相互作用因子の網羅的解析を行う予定である。またこれと並行して、取得された複数のnnk1-35変異株のTS相補株についてもそれぞれ全ゲノムシーケンス解析を実施し、TSの相補に関わる原因遺伝子の同定を目指す。これらの解析から得られたデータの共通項となる因子を絞り込み、Nnk1タンパク質の生理学的機能を明らかにする予定である。

  3. Elucidation of the lifespan control mechanism by a novel kinase Nnk1 in fission yeast

    Grant number:21K14769  2021.4 - 2024.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

    Shimasaki Takafumi

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    Authorship:Principal investigator 

    Grant amount:\4550000 ( Direct Cost: \3500000 、 Indirect Cost:\1050000 )

    In this study, we performed a functional analysis of the Nnk1 protein, which is involved in the control of chronological lifespan in fission yeast. The Nnk1 protein contains a kinase domain in the C-terminal region, but its phosphorylation substrates and physiological functions have not been elucidated. The analysis revealed that the Nnk1 protein is involved in cell wall stress response and is required for the activation of Pmk1 MAPK, which is important for the response. In addition, phosphorylation proteomic analysis revealed that decreased activity of the Nnk1 protein reduces the phosphorylation levels of several nutrient transporters.

 

Teaching Experience (On-campus) 12

  1. Biological Science Research Course (Advanced Course)

    2021

  2. Seminar in Life Science IIC

    2021

  3. Seminar in Life Science IIA

    2021

  4. Specific Lecture for Advanced Pharmaceutical Sciences

    2021

  5. Biological Science Research Course

    2021

  6. Seminar in Biological Science ⅠB

    2021

  7. Seminar in Biological Science ⅠA

    2021

  8. Basic Training for Crossover Research Course

    2021

  9. Basic Training for Crossover Research

    2021

  10. Seminar in Life Science IID

    2021

  11. Seminar in Life Science IIB

    2021

  12. 応用生命科学実験実習

    2020

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