2024/04/22 更新

写真a

シマサキ タカフミ
島崎 嵩史
SHIMASAKI Takafumi
所属
大学院創薬科学研究科 基盤創薬学専攻 助教
大学院担当
大学院創薬科学研究科
学部担当
農学部 応用生命科学科
職名
助教
連絡先
メールアドレス

学位 1

  1. 博士(創薬科学) ( 2017年3月   名古屋大学 ) 

経歴 1

  1. 名古屋大学   農学部   助教

    2018年4月 - 現在

所属学協会 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

委員歴 1

  1. 日本農芸化学会中部支部   会計幹事  

    2021年3月 - 2023年2月   

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    団体区分:学協会

 

論文 24

  1. Low-Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. 査読有り

    Ohtsuka H, Shimasaki T, Aiba H

    Advanced biology     頁: e2400138   2024年4月

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    記述言語:英語  

    DOI: 10.1002/adbi.202400138

    PubMed

  2. Identification of <i>plb1</i> mutation that extends longevity via activating Sty1 MAPK in <i>Schizosaccharomyces pombe</i> 査読有り

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

    MOLECULAR GENETICS AND GENOMICS   299 巻 ( 1 ) 頁: 20   2024年2月

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    記述言語:英語   出版者・発行元: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+ gene. plb1+ 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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  3. <i>ecl</i> family genes: Factors linking starvation and lifespan extension in <i>Schizosaccharomyces pombe</i>

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

    MOLECULAR MICROBIOLOGY   120 巻 ( 5 ) 頁: 645 - 657   2023年11月

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    記述言語:英語   出版者・発行元:Molecular Microbiology  

    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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  4. Metarhizium robertsii COH1 functionally complements Schizosaccharomyces pombe Ecl family proteins. 査読有り

    Ohtsuka H, Kawai S, Otsubo Y, Shimasaki T, Yamashita A, Aiba H

    The Journal of general and applied microbiology   advpub 巻 ( 0 )   2023年10月

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    記述言語:英語   出版者・発行元:公益財団法人 応用微生物学・分子細胞生物学研究奨励会  

    DOI: 10.2323/jgam.2023.09.001

    PubMed

    CiNii Research

  5. The ecl family gene ecl3<SUP>+</SUP> is induced by phosphate starvation and contributes to sexual differentiation in fission yeast 査読有り

    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   136 巻 ( 6 )   2023年3月

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    記述言語:英語   出版者・発行元:Journal of Cell Science  

    In Schizosaccharomyces pombe, ecl family genes are induced by several signals, such as starvation of various nutrients, including sulfur, amino acids and Mg2+, 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+ remain unidentified. We demonstrate that ecl3+ is induced by phosphate starvation, similar to its chromosomally neighboring genes, pho1+ and pho84+, which respectively encode an extracellular acid phosphatase and an inorganic phosphate transporter. ecl3+ 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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  6. Sporulation: A response to starvation in the fission yeast <i>Schizosaccharomyces pombe</i> 査読有り

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

    MICROBIOLOGYOPEN   11 巻 ( 3 ) 頁: e1303   2022年6月

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    記述言語:英語   出版者・発行元:MicrobiologyOpen  

    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 G0 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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  7. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast 査読有り

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

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   86 巻 ( 6 ) 頁: 775 - 779   2022年5月

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    記述言語:英語   出版者・発行元: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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  8. Response to leucine in <i>Schizosaccharomyces pombe</i> (fission yeast) 査読有り

    Ohtsuka, H; Shimasaki, T; Aiba, H

    FEMS YEAST RESEARCH   22 巻 ( 1 )   2022年4月

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    記述言語:英語   出版者・発行元:FEMS Yeast Research  

    Leucine (Leu) is a branched-chain, essential amino acid in animals, including humans. Fungi, including the fission yeast Schizosaccharomyces pombe, can biosynthesize Leu, but deletion of any of the genes in this biosynthesis leads to Leu auxotrophy. In this yeast, although a mutation in the Leu biosynthetic pathway, leu1-32, is clearly inconvenient for this species, it has increased its usefulness as a model organism in laboratories worldwide. Leu auxotrophy produces intracellular responses and phenotypes different from those of the prototrophic strains, depending on the growing environment, which necessitates a certain degree of caution in the analysis and interpretation of the experimental results. Under amino acid starvation, the amino acid-auxotrophic yeast induces cellular responses, which are conserved in higher organisms without the ability of synthesizing amino acids. This mini-review focuses on the roles of Leu in S. pombe and discusses biosynthetic pathways, contribution to experimental convenience using a plasmid specific for Leu auxotrophic yeast, signaling pathways, and phenotypes caused by Leu starvation. An accurate understanding of the intracellular responses brought about by Leu auxotrophy can contribute to research in various fields using this model organism and to the understanding of intracellular responses in higher organisms that cannot synthesize Leu.

    DOI: 10.1093/femsyr/foac020

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

    Maruyama, T; Hayashi, K; Matsui, K; Maekawa, Y; Shimasaki, T; Ohtsuka, H; Saitoh, S; Aiba, H

    JOURNAL OF GENERAL AND APPLIED MICROBIOLOGY   68 巻 ( 6 ) 頁: 270 - 277   2022年

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    記述言語:英語   出版者・発行元:Journal of General and Applied Microbiology  

    Fission yeast, Schizosaccharomyces pombe, possesses eight hexose transporters, Ght1~8. In order to clar-ify the role of each hexose transporter on glucose uptake, a glucose uptake assay system was estab-lished and the actual glucose uptake activity of each hexose transporter-deletion mutant was measured. Under normal growth condition containing 2% glucose, ∆ght5 and ∆ght2 mutants showed large and small decrease in glucose uptake activity, respec-tively. 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 ∆ght5 mutant showed a significant lifespan extension. Based on these results we showed that Ght5 is mainly involved in the glucose uptake in Schizosaccharomyces pombe, and suggested that the ∆ght5 mutant has prolonged lifespan due to physiological changes similar to calorie restriction.

    DOI: 10.2323/jgam.2022.05.006

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  10. Identification of <i>ksg1</i> mutation showing long-lived phenotype in fission yeast 査読有り

    Matsui, K; Okamoto, K; Hasegawa, T; Ohtsuka, H; Shimasaki, T; Ihara, K; Goto, Y; Aoki, K; Aiba, H

    GENES TO CELLS   26 巻 ( 12 ) 頁: 967 - 978   2021年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Genes to Cells  

    Fission yeast is a good model organism for the study of lifespan. To elucidate the mechanism, we screened for long-lived mutants. We found a nonsense mutation in the ksg1+ gene, which encodes an ortholog of mammalian PDK1 (phosphoinositide-dependent protein kinase). The mutation was in the PH domain of Ksg1 and caused defect in membrane localization and protein stability. Analysis of the ksg1 mutant revealed that the reduced amounts and/or activity of the Ksg1 protein are responsible for the increased lifespan. Ksg1 is essential for growth and known to phosphorylate multiple substrates, but the substrate responsible for the long-lived phenotype of ksg1 mutation is not yet known. Genetic analysis showed that deletion of pck2 suppressed the long-lived phenotype of ksg1 mutant, suggesting that Pck2 might be involved in the lifespan extension caused by ksg1 mutation.

    DOI: 10.1111/gtc.12897

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  11. Response to sulfur in <i>Schizosaccharomyces pombe</i> 査読有り

    Ohtsuka, H; Shimasaki, T; Aiba, H

    FEMS YEAST RESEARCH   21 巻 ( 5 )   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FEMS Yeast Research  

    Sulfur is an essential component of various biologically important molecules, including methionine, cysteine and glutathione, and it is also involved in coping with oxidative and heavy metal stress. Studies using model organisms, including budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe), have contributed not only to understanding various cellular processes but also to understanding the utilization and response mechanisms of each nutrient, including sulfur. Although fission yeast can use sulfate as a sulfur source, its sulfur metabolism pathway is slightly different from that of budding yeast because it does not have a trans-sulfuration pathway. In recent years, it has been found that sulfur starvation causes various cellular responses in S. pombe, including sporulation, cell cycle arrest at G2, chronological lifespan extension, autophagy induction and reduced translation. This MiniReview identifies two sulfate transporters in S. pombe, Sul1 (encoded by SPBC3H7.02) and Sul2 (encoded by SPAC869.05c), and summarizes the metabolic pathways of sulfur assimilation and cellular response to sulfur starvation. Understanding these responses, including metabolism and adaptation, will contribute to a better understanding of the various stress and nutrient starvation responses and chronological lifespan regulation caused by sulfur starvation.

    DOI: 10.1093/femsyr/foab041

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  12. Extension of chronological lifespan in <i>Schizosaccharomyces pombe</i> 査読有り

    Ohtsuka, H; Shimasaki, T; Aiba, H

    GENES TO CELLS   26 巻 ( 7 ) 頁: 459 - 473   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Genes to Cells  

    There are several examples in the nature wherein the mechanism of longevity control of unicellular organisms is evolutionarily conserved with that of higher multicellular organisms. The present microreview focuses on aging and longevity studies, particularly on chronological lifespan (CLS) concerning the unicellular eukaryotic fission yeast Schizosaccharomyces pombe. In S. pombe, >30 compounds, 8 types of nutrient restriction, and >80 genes that extend CLS have been reported. Several CLS control mechanisms are known to be involved in nutritional response, energy utilization, stress responses, translation, autophagy, and sexual differentiation. In unicellular organisms, the control of CLS is directly linked to the mechanism by which cells are maintained in limited-resource environments, and their genetic information is left to posterity. We believe that this important mechanism may have been preserved as a lifespan control mechanism for higher organisms.

    DOI: 10.1111/gtc.12854

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  13. Identification of <i>sur2</i> mutation affecting the lifespan of fission yeast 査読有り

    Kurauchi, T; Matsui, K; Shimasaki, T; Ohtsuka, H; Tsubouchi, S; Ihara, K; Tani, M; Aiba, H

    FEMS MICROBIOLOGY LETTERS   368 巻 ( 12 )   2021年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FEMS Microbiology Letters  

    Yeast is a suitable model system to analyze the mechanism of lifespan. In this study, to identify novel factors involved in chronological lifespan, we isolated a mutant with a long chronological lifespan and found a missense mutation in the sur2+ gene, which encodes a homolog of Saccharomyces cerevisiae sphingolipid C4-hydroxylase in fission yeast. Characterization of the mutant revealed that loss of sur2 function resulted in an extended chronological lifespan. The effect of caloric restriction, a well-known signal for extending lifespan, is thought to be dependent on the sur2+ gene.

    DOI: 10.1093/femsle/fnab070

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  14. Genes affecting the extension of chronological lifespan in <i>Schizosaccharomyces pombe</i> (fission yeast) 査読有り

    Ohtsuka, H; Shimasaki, T; Aiba, H

    MOLECULAR MICROBIOLOGY   115 巻 ( 4 ) 頁: 623 - 642   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Molecular Microbiology  

    So far, more than 70 genes involved in the chronological lifespan (CLS) of Schizosaccharomyces pombe (fission yeast) have been reported. In this mini-review, we arrange and summarize these genes based on the reported genetic interactions between them and the physical interactions between their products. We describe the signal transduction pathways that affect CLS in S. pombe: target of rapamycin complex 1, cAMP-dependent protein kinase, Sty1, and Pmk1 pathways have important functions in the regulation of CLS extension. Furthermore, the Php transcription complex, Ecl1 family proteins, cyclin Clg1, and the cyclin-dependent kinase Pef1 are important for the regulation of CLS extension in S. pombe. Most of the known genes involved in CLS extension are related to these pathways and genes. In this review, we focus on the individual genes regulating CLS extension in S. pombe and discuss the interactions among them.

    DOI: 10.1111/mmi.14627

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  15. Magnesium depletion extends fission yeast lifespan via general amino acid control activation 査読有り

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

    MICROBIOLOGYOPEN   10 巻 ( 2 ) 頁: e1176   2021年3月

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    記述言語:英語   出版者・発行元:MicrobiologyOpen  

    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 (Mg2+) depletion extends CLS of the fission yeast Schizosaccharomyces pombe through a mechanism involving the Ecl1 gene family. We discovered that ecl1+ expression, which extends CLS, responds to Mg2+ depletion. Therefore, we investigated the underlying intracellular responses. In amino acid auxotrophic strains, Mg2+ depletion robustly induces ecl1+ 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 Mg2+ depletion and its influence on the mechanism controlling longevity.

    DOI: 10.1002/mbo3.1176

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  16. Tschimganine has different targets for chronological lifespan extension and growth inhibition in fission yeast 査読有り

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

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY     2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  17. Cdc13 (cyclin B) is degraded by autophagy under sulfur depletion in fission yeast 査読有り

    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年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

  18. Sulfur depletion induces autophagy through Ecl1 family genes in fission yeast 査読有り

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

    GENES TO CELLS   25 巻 ( 12 ) 頁: 825 - 830   2020年12月

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    記述言語:英語   出版者・発行元:Genes to Cells  

    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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  19. <i>gas1</i> mutation extends chronological lifespan via Pmk1 and Sty1 MAPKs in <i>Schizosaccharomyces pombe</i> 査読有り

    Imai, Y; Shimasaki, T; Enokimura, C; Ohtsuka, H; Tsubouchi, S; Ihara, K; Aiba, H

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   84 巻 ( 2 ) 頁: 330 - 337   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Bioscience, Biotechnology and Biochemistry  

    In the longevity research by using yeasts, chronological lifespan is defined as the survival time after entry into stationary phase. Previously, screening for long lived mutants of Schizosaccharomyces pombe was performed to identify the novel factors involved in longevity. From this screening, one long lived mutant called as No.36 was obtained. In this study, we identified the mutation caused in gas1+, which encodes glucanosyltransferase (gas1-287 mutation) is responsible for the longevity of No.36 mutant. Through the analysis of this mutant, we found that cell wall perturbing agent micafungin also extends chronological lifespan in fission yeast. This lifespan extension depended on both Pmk1 and Sty1 MAP kinases, and longevity caused by the gas1-287 mutation also depended on these kinases. In summary, we propose that the gas1-287 mutation causes longevity as the similar mechanism as cell wall stress depending on Pmk1 and Sty1 MAPK pathways.

    DOI: 10.1080/09168451.2019.1676695

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  20. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1 査読有り

    Ohtsuka, H; Kato, T; Sato, T; Shimasaki, T; Kojima, T; Aiba, H

    MOLECULAR GENETICS AND GENOMICS   294 巻 ( 6 ) 頁: 1499 - 1509   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Molecular Genetics and Genomics  

    Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. In Schizosaccharomyces pombe, the Ecl1 family genes have been associated with lifespan control and are necessary for cell responses to nutrient depletion, but their functions and mechanisms of action remain uncharacterized. Herein, we show that leucine depletion extends the chronological lifespan (CLS) of leucine-auxotrophic cells. Furthermore, depletion of leucine extended CLS and caused cell miniaturization and cell cycle arrest at the G1 phase, and all of these processes depended on Ecl1 family genes. Although depletion of leucine raises the expression of ecl1+ by about 100-fold in leucine-auxotrophic cells, these conditions did not affect ecl1+ expression in leucine-auxotrophic fil1 mutants that were isolated in deletion set screens using 79 mutants disrupting a transcription factor. Fil1 is a GATA-type zinc finger transcription factor that reportedly binds directly to the upstream regions of ecl1+ and ecl2+. Accordingly, we suggest that Ecl1 family genes are induced in response to environmental stresses, such as oxidative stress and heat stress, or by nutritional depletion of nitrogen or sulfur sources or the amino acid leucine. We also propose that these genes play important roles in the maintenance of cell survival until conditions that favor proliferation are restored.

    DOI: 10.1007/s00438-019-01592-6

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  21. Tschimganine and its derivatives extend the chronological life span of yeast via activation of the Sty1 pathway 査読有り

    Hibi, T; Ohtsuka, H; Shimasaki, T; Inui, S; Shibuya, M; Tatsukawa, H; Kanie, K; Yamamoto, Y; Aiba, H

    GENES TO CELLS   23 巻 ( 8 ) 頁: 620 - 637   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Genes to Cells  

    Most antiaging factors or life span extenders are associated with calorie restriction (CR). Very few of these factors function independently of, or additively with, CR. In this study, we focused on tschimganine, a compound that was reported to extend chronological life span (CLS). Although tschimganine led to the extension of CLS, it also inhibited yeast cell growth. We acquired a Schizosaccharomyces pombe mutant with a tolerance for tschimganine due to the gene crm1. The resulting Crm1 protein appears to export the stress-activated protein kinase Sty1 from the nucleus to the cytosol even under stressful conditions. Furthermore, we synthesized two derivative compounds of tschimganine, α-hibitakanine and β-hibitakanine; these derivatives did not inhibit cell growth, as seen with tschimganine. α-hibitakanine extended the CLS, not only in S. pombe but also in Saccharomyces cerevisiae, indicating the possibility that life span regulation by tschimganine derivative may be conserved across various yeast species. We found that the longevity induced by tschimganine was dependent on the Sty1 pathway. Based on our results, we propose that tschimganine and its derivatives extend CLS by activating the Sty1 pathway in fission yeast, and CR extends CLS via two distinct pathways, one Sty1-dependent and the other Sty1-independent. These findings provide the potential for creating an additive life span extension effect when combined with CR, as well as a better understanding of the mechanism of CLS.

    DOI: 10.1111/gtc.12604

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  22. Sulfur restriction extends fission yeast chronological lifespan through Ecl1 family genes by downregulation of ribosome 査読有り

    Ohtsuka, H; Takinami, M; Shimasaki, T; Hibi, T; Murakami, H; Aiba, H

    MOLECULAR MICROBIOLOGY   105 巻 ( 1 ) 頁: 84 - 97   2017年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Molecular Microbiology  

    Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1+ gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner.

    DOI: 10.1111/mmi.13686

    Web of Science

    Scopus

    PubMed

  23. Ecl1 is a zinc-binding protein involved in the zinc-limitation-dependent extension of chronological life span in fission yeast 査読有り

    Shimasaki, T; Ohtsuka, H; Naito, C; Azuma, K; Tenno, T; Hiroaki, H; Murakami, H; Aiba, H

    MOLECULAR GENETICS AND GENOMICS   292 巻 ( 2 ) 頁: 475 - 481   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Molecular Genetics and Genomics  

    Overexpression of Ecl1-family genes (ecl1+, ecl2+, and ecl3+) results in the extension of the chronological life span in Schizosaccharomyces pombe. However, the mechanism for this extension has not been defined clearly. Ecl1-family proteins consist of approximately 80 amino acids, and four cysteine residues are conserved in their N-terminal domains. This study focused on the Ecl1 protein, mutating its cysteine residues sequentially to confirm their importance. As a result, all mutated Ecl1 proteins nearly lost the function to extend the chronological life span, suggesting that these four cysteine residues are essential for the Ecl1 protein. Utilizing ICP-AES (inductively coupled plasma atomic emission spectroscopy) analysis, we found that wild-type Ecl1 proteins contain zinc, while cysteine-mutated Ecl1 proteins do not. We also analyzed the effect of environmental zinc on the chronological life span. We found that zinc limitation extends the chronological life span, and this extension depends on the Ecl1-family proteins.

    DOI: 10.1007/s00438-016-1285-x

    Web of Science

    Scopus

    PubMed

  24. Ecl1 is activated by the transcription factor Atf1 in response to H2O2 stress in Schizosaccharomyces pombe 査読有り

        2014年4月

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講演・口頭発表等 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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    開催年月日: 2020年12月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:福岡   国名:日本国  

  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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:Web開催   国名:日本国  

  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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:Web開催   国名:日本国  

  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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:Web開催   国名:日本国  

  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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:Web開催   国名:日本国  

  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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    開催年月日: 2020年9月

    会議種別:口頭発表(一般)  

    開催地:Web開催   国名:日本国  

  7. 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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:Web開催   国名:日本国  

  8. 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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:Web開催   国名:日本国  

  9. 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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:Web開催   国名:日本国  

  10. 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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    開催年月日: 2020年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:Web開催   国名:日本国  

  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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    開催年月日: 2020年3月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:名古屋   国名:日本国  

  12. 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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    開催年月日: 2020年3月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:名古屋   国名:日本国  

  13. 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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    開催年月日: 2020年3月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:名古屋   国名:日本国  

  14. 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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    開催年月日: 2020年3月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:名古屋   国名:日本国  

  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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    開催年月日: 2019年12月

    記述言語:日本語   会議種別:ポスター発表  

    開催地:福岡   国名:日本国  

  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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    開催年月日: 2019年9月

    記述言語:日本語   会議種別:ポスター発表  

    開催地: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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    開催年月日: 2019年9月

    記述言語:日本語   会議種別:口頭発表(一般)  

    開催地:静岡市清水文化会館マリナート   国名:日本国  

  18. Leucine depletion extends the lifespans of fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. 国際会議

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

    The 10 th International Fission Yeast Meeting  

     詳細を見る

    開催年月日: 2019年7月

    記述言語:英語   会議種別:ポスター発表  

    開催地:Barcelona, Spain   国名:スペイン  

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科研費 2

  1. 細胞周期制御に関わる新規寿命関連因子の機能解明

    研究課題/研究課題番号:23K13868  2023年4月 - 2025年3月

    科学研究費助成事業  若手研究

    島崎 嵩史

      詳細を見る

    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    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。

  2. 分裂酵母における新規キナーゼNnk1による寿命制御機構の解明

    研究課題/研究課題番号:21K14769  2021年4月 - 2024年3月

    科学研究費助成事業  若手研究

    島崎 嵩史

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    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    本研究では、分裂酵母における新規の寿命制御因子であるNnk1タンパク質の生理学的機能、およびその寿命制御メカニズムの解明を行う。分裂酵母は基本的な細胞内メカニズムが高等生物と類似しており、種々の寿命制御因子(カロリー制限応答、PKA、TORなど)も保存されており、優れた寿命研究モデルである。分裂酵母におけるNnk1タンパク質による寿命制御メカニズムの解明を通して、高等生物の寿命制御の理解に寄与する知見を得ることを目指す。
    本研究では、分裂酵母における新規寿命関連因子Nnk1による寿命制御機構の解明を目指し、解析を行っている。nnk1+遺伝子は分裂酵母の生育に必須であり、コードしているタンパク質内にはキナーゼドメインと予測される配列が存在しているが、Nnk1タンパク質の基質や生理学的機能については今のところ明らかになっていない。しかしながら過去に、新規寿命制御因子の同定を目的とした長寿命変異株のスクリーニングが行われ、nnk1+遺伝子において生じた変異(nnk1-35 変異)が経時寿命の延長を引き起こすことが明らかとなっている。本研究ではこのNnk1タンパク質の標的基質および下流で機能する因子を明らかにし、Nnk1タンパク質による未知の寿命制御機構の解明を目指し、より高等な生物種の寿命制御機構の解明に寄与する可能性のある新たな知見を得ることを目的としている。解析にあたって、まずはnnk1-35変異の近傍にkanRを導入した株が顕著な高温感受性を示したため、この株に分裂酵母のプラスミドゲノムライブラリーを導入し、高温感受性を回復するスクリーニングを実施した。その結果、いくつか高温感受性を回復する株が取得されたが、いずれの株のプラスミドにも野生型のnnk1+遺伝子がコードされており、Nnk1以外の新規の因子の同定には至らなかった。Nnk1タンパク質のリン酸化基質の同定に関しては、nnk1-35変異株において細胞壁ストレス応答に関与するMAPKの一種であるPmk1のリン酸化レベルが低下することを新たに見出した。
    作製したnnk1-35-kanR変異株に顕著な高温感受性が観察されたため、ゲノムライブラリープラスミドを導入することでこの表現型を回復する因子のスクリーニングを進めていた。その後、この高温感受性を回復した株がいくつか取得されたが、表現型の回復に関与する遺伝子の同定をシーケンス解析によって進めた結果、いずれも野生型のnnk1+遺伝子がコードされていたため新規の遺伝子の同定には至っていない。Nnk1タンパク質のリン酸化基質の同定に関しては、Pmk1が1つの候補として同定されたため、直接的にリン酸化が行われるか等について検証を進めている。。
    今後は引き続き、nnk1変異株由来のゲノムライブラリーを用いたnnk1-35-kanR変異株の温度感受性を相補する因子の取得と同定を目指す。Nnk1のリン酸化基質の同定に関しては、Pmk1が1つの候補として同定されたため、Pmk1のリン酸化に関与する具体的なメカニズムについて解析を行っている。また、その他のリン酸化基質の同定についても引き続き網羅的な解析を続ける予定である。今後、これらの解析結果をまとめた上で、論文発表や学会発表を行う予定である。

 

担当経験のある科目 (本学) 12

  1. 創薬生物科学実習

    2021

  2. 創薬生物科学セミナーⅡC

    2021

  3. 創薬生物科学セミナーⅡA

    2021

  4. 先端薬科学特論

    2021

  5. 創薬生物科学実験

    2021

  6. 創薬生物科学セミナーⅠB

    2021

  7. 創薬生物科学セミナーⅠA

    2021

  8. 創薬生物科学セミナーⅡD

    2021

  9. 創薬生物科学セミナーⅡB

    2021

  10. 多分野融合実践実習

    2021

  11. 多分野融合実践演習

    2021

  12. 応用生命科学実験実習

    2020

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