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  1. Article ; Online: Contribution of the yeast bi-chaperone system in the restoration of the RNA helicase Ded1 and translational activity under severe ethanol stress.

    Ando, Ryoko / Ishikawa, Yu / Kamada, Yoshiaki / Izawa, Shingo

    The Journal of biological chemistry

    2023  Volume 299, Issue 12, Page(s) 105472

    Abstract: Preexposure to mild stress often improves cellular tolerance to subsequent severe stress. Severe ethanol stress (10% v/v) causes persistent and pronounced translation repression in Saccharomyces cerevisiae. However, it remains unclear whether preexposure ...

    Abstract Preexposure to mild stress often improves cellular tolerance to subsequent severe stress. Severe ethanol stress (10% v/v) causes persistent and pronounced translation repression in Saccharomyces cerevisiae. However, it remains unclear whether preexposure to mild stress can mitigate translation repression in yeast cells under severe ethanol stress. We found that the translational activity of yeast cells pretreated with 6% (v/v) ethanol was initially significantly repressed under subsequent 10% ethanol but was then gradually restored even under severe ethanol stress. We also found that 10% ethanol caused the aggregation of Ded1, which plays a key role in translation initiation as a DEAD-box RNA helicase. Pretreatment with 6% ethanol led to the gradual disaggregation of Ded1 under subsequent 10% ethanol treatment in wild-type cells but not in fes1Δhsp104Δ cells, which are deficient in Hsp104 with significantly reduced capacity for Hsp70. Hsp104 and Hsp70 are key components of the bi-chaperone system that play a role in yeast protein quality control. fes1Δhsp104Δ cells did not restore translational activity under 10% ethanol, even after pretreatment with 6% ethanol. These results indicate that the regeneration of Ded1 through the bi-chaperone system leads to the gradual restoration of translational activity under continuous severe stress. This study provides new insights into the acquired tolerance of yeast cells to severe ethanol stress and the resilience of their translational activity.
    MeSH term(s) DEAD-box RNA Helicases/genetics ; DEAD-box RNA Helicases/metabolism ; Ethanol/pharmacology ; Protein Biosynthesis ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances DEAD-box RNA Helicases (EC 3.6.4.13) ; Ethanol (3K9958V90M) ; Saccharomyces cerevisiae Proteins ; DED1 protein, S cerevisiae (EC 3.6.1.-)
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.105472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Yeast Tor complex 1 phosphorylates eIF4E-binding protein, Caf20.

    Kamada, Yoshiaki / Ando, Ryoko / Izawa, Shingo / Matsuura, Akira

    Genes to cells : devoted to molecular & cellular mechanisms

    2023  Volume 28, Issue 11, Page(s) 789–799

    Abstract: Tor complex 1 (TORC1), a master regulator of cell growth, is an evolutionarily conserved protein kinase within eukaryotic organisms. To control cell growth, TORC1 governs translational processes by phosphorylating its substrate proteins in response to ... ...

    Abstract Tor complex 1 (TORC1), a master regulator of cell growth, is an evolutionarily conserved protein kinase within eukaryotic organisms. To control cell growth, TORC1 governs translational processes by phosphorylating its substrate proteins in response to cellular nutritional cues. Mammalian TORC1 (mTORC1) assumes the responsibility of phosphorylating the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) to regulate its interaction with eIF4E. The budding yeast Saccharomyces cerevisiae possesses a pair of 4E-BP genes, CAF20 and EAP1. However, the extent to which the TORC1-4E-BP axis regulates translational initiation in yeast remains uncertain. In this study, we demonstrated the influence of TORC1 on the phosphorylation status of Caf20 in vivo, as well as the direct phosphorylation of Caf20 by TORC1 in vitro. Furthermore, we found the TORC1-dependent recruitment of Caf20 to the 80S ribosome. Consequently, our study proposes a plausible involvement of yeast's 4E-BP in the efficacy of translation initiation, an aspect under the control of TORC1.
    MeSH term(s) Animals ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Protein Binding ; Peptide Initiation Factors/genetics ; Peptide Initiation Factors/metabolism ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Phosphoproteins/metabolism ; Protein Biosynthesis ; Phosphorylation ; Mammals/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Peptide Initiation Factors ; Cell Cycle Proteins ; Phosphoproteins ; Caf20 protein, S cerevisiae ; Transcription Factors ; Saccharomyces cerevisiae Proteins
    Language English
    Publishing date 2023-09-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 1330000-3
    ISSN 1365-2443 ; 1356-9597
    ISSN (online) 1365-2443
    ISSN 1356-9597
    DOI 10.1111/gtc.13067
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  3. Article ; Online: Novel tRNA function in amino acid sensing of yeast Tor complex1.

    Kamada, Yoshiaki

    Genes to cells : devoted to molecular & cellular mechanisms

    2017  Volume 22, Issue 2, Page(s) 135–147

    Abstract: TOR complex1 (TORC1), a master regulator of cell growth, is regulated by amino acids. Amino acids are fundamental nutrients, and 20 species of amino acids building proteins are not interchangeable with each other. Therefore, TORC1 should sense each amino ...

    Abstract TOR complex1 (TORC1), a master regulator of cell growth, is regulated by amino acids. Amino acids are fundamental nutrients, and 20 species of amino acids building proteins are not interchangeable with each other. Therefore, TORC1 should sense each amino acid individually. Mammalian mTORC1 is controlled by Rag GTPases and their regulators. However, Rag factors are dispensable for amino acid sensing by TORC1 in the budding yeast, suggesting an alternative mechanism of TORC1 regulation. Here, genetic investigation discovered the involvement of (aminoacyl-)tRNA ((aa-)tRNA) in TORC1 regulation. Biochemical TORC1 assay also showed that tRNA directly inhibits TORC1 kinase activity. Reducing cellular tRNA molecule desensitizes TORC1 inactivation by nitrogen starvation in vivo. Based on these results, I propose a model of the TORC1 regulatory mechanism in which free tRNA released from protein synthesis under amino acid starvation inhibits TORC1 activity. Therefore, TORC1 uses tRNA-mediated mechanism and Rag factors in parallel to sense intracellular amino acids.
    MeSH term(s) Amino Acids/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Monomeric GTP-Binding Proteins/metabolism ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction/physiology ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Yeasts/genetics ; Yeasts/metabolism
    Chemical Substances Amino Acids ; Multiprotein Complexes ; Saccharomyces cerevisiae Proteins ; TORC1 protein complex, S cerevisiae ; Transcription Factors ; RNA, Transfer (9014-25-9) ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2017-02
    Publishing country England
    Document type Journal Article
    ZDB-ID 1330000-3
    ISSN 1365-2443 ; 1356-9597
    ISSN (online) 1365-2443
    ISSN 1356-9597
    DOI 10.1111/gtc.12462
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Structure-based engineering of Tor complexes reveals that two types of yeast TORC1 produce distinct phenotypes.

    Kamada, Yoshiaki / Umeda, Chiharu / Mukai, Yukio / Ohtsuka, Hokuto / Otsubo, Yoko / Yamashita, Akira / Kosugi, Takahiro

    Journal of cell science

    2024  Volume 137, Issue 4

    Abstract: Certain proteins assemble into diverse complex states, each having a distinct and unique function in the cell. Target of rapamycin (Tor) complex 1 (TORC1) plays a central role in signalling pathways that allow cells to respond to the environment, ... ...

    Abstract Certain proteins assemble into diverse complex states, each having a distinct and unique function in the cell. Target of rapamycin (Tor) complex 1 (TORC1) plays a central role in signalling pathways that allow cells to respond to the environment, including nutritional status signalling. TORC1 is widely recognised for its association with various diseases. The budding yeast Saccharomyces cerevisiae has two types of TORC1, Tor1-containing TORC1 and Tor2-containing TORC1, which comprise different constituent proteins but are considered to have the same function. Here, we computationally modelled the relevant complex structures and then, based on the structures, rationally engineered a Tor2 mutant that could form Tor complex 2 (TORC2) but not TORC1, resulting in a redesign of the complex states. Functional analysis of the Tor2 mutant revealed that the two types of TORC1 induce different phenotypes, with changes observed in rapamycin, caffeine and pH dependencies of cell growth, as well as in replicative and chronological lifespan. These findings uncovered by a general approach with huge potential - model structure-based engineering - are expected to provide further insights into various fields such as molecular evolution and lifespan.
    MeSH term(s) Saccharomyces cerevisiae/genetics ; Saccharomycetales ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 2 ; Phenotype ; Sirolimus
    Chemical Substances Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; Mechanistic Target of Rapamycin Complex 2 (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2024-02-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2993-2
    ISSN 1477-9137 ; 0021-9533
    ISSN (online) 1477-9137
    ISSN 0021-9533
    DOI 10.1242/jcs.261625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae

    Sekiguchi, Takeshi / Ishii, Takashi / Kamada, Yoshiaki / Funakoshi, Minoru / Kobayashi, Hideki / Furuno, Nobuaki

    Biochemical and biophysical research communications. 2022 Apr. 02, v. 598

    2022  

    Abstract: 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 ... ...

    Abstract 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.
    Keywords GTPase-activating proteins ; Saccharomyces cerevisiae ; amino acids ; autophagy ; genes ; guanosine ; guanosine triphosphate ; guanosinetriphosphatase ; hydrogen peroxide ; oxidative stress ; phenotype ; protein synthesis ; research ; stress response ; yeasts
    Language English
    Dates of publication 2022-0402
    Size p. 107-112.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 205723-2
    ISSN 0006-291X ; 0006-291X
    ISSN (online) 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.02.016
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  6. Article ; Online: Novel Links between TORC1 and Traditional Non-Coding RNA, tRNA.

    Otsubo, Yoko / Kamada, Yoshiaki / Yamashita, Akira

    Genes

    2020  Volume 11, Issue 9

    Abstract: Target of rapamycin (TOR) is a serine/threonine kinase that modulates cell growth and metabolism in response to environmental changes. Transfer RNA (tRNA) is an abundant and ubiquitous small non-coding RNA that is essential in the translation of mRNAs. ... ...

    Abstract Target of rapamycin (TOR) is a serine/threonine kinase that modulates cell growth and metabolism in response to environmental changes. Transfer RNA (tRNA) is an abundant and ubiquitous small non-coding RNA that is essential in the translation of mRNAs. Beyond its canonical role, it has been revealed that tRNAs have more diverse functions. TOR complex 1 (TORC1), which is one of the two TOR complexes, regulates tRNA synthesis by controlling RNA polymerase III. In addition to tRNA synthesis regulation, recent studies have revealed hidden connections between TORC1 and tRNA, which are both essential players in eukaryotic cellular activities. Here, we review the accumulating findings on the regulatory links between TORC1 and tRNA-particularly those links in the budding yeast
    MeSH term(s) Gene Expression Regulation, Fungal ; Mechanistic Target of Rapamycin Complex 1/genetics ; Mechanistic Target of Rapamycin Complex 1/metabolism ; RNA, Transfer/genetics ; RNA, Transfer/metabolism ; RNA, Untranslated/genetics ; RNA, Untranslated/metabolism ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/growth & development ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/growth & development ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; Schizosaccharomyces pombe Proteins/metabolism
    Chemical Substances RNA, Untranslated ; Saccharomyces cerevisiae Proteins ; Schizosaccharomyces pombe Proteins ; RNA, Transfer (9014-25-9) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1)
    Language English
    Publishing date 2020-08-19
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425 ; 2073-4425
    ISSN (online) 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes11090956
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  7. Article: Novel Links between TORC1 and Traditional Non-Coding RNA, tRNA

    Otsubo, Yoko / Kamada, Yoshiaki / Yamashita, Akira

    Genes. 2020 Aug. 19, v. 11, no. 9

    2020  

    Abstract: Target of rapamycin (TOR) is a serine/threonine kinase that modulates cell growth and metabolism in response to environmental changes. Transfer RNA (tRNA) is an abundant and ubiquitous small non-coding RNA that is essential in the translation of mRNAs. ... ...

    Abstract Target of rapamycin (TOR) is a serine/threonine kinase that modulates cell growth and metabolism in response to environmental changes. Transfer RNA (tRNA) is an abundant and ubiquitous small non-coding RNA that is essential in the translation of mRNAs. Beyond its canonical role, it has been revealed that tRNAs have more diverse functions. TOR complex 1 (TORC1), which is one of the two TOR complexes, regulates tRNA synthesis by controlling RNA polymerase III. In addition to tRNA synthesis regulation, recent studies have revealed hidden connections between TORC1 and tRNA, which are both essential players in eukaryotic cellular activities. Here, we review the accumulating findings on the regulatory links between TORC1 and tRNA—particularly those links in the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe.
    Keywords DNA-directed RNA polymerase ; Saccharomyces cerevisiae ; Schizosaccharomyces pombe ; cell growth ; messenger RNA ; metabolism ; non-coding RNA ; protein-serine-threonine kinases ; rapamycin ; transfer RNA ; translation (genetics) ; yeasts
    Language English
    Dates of publication 2020-0819
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes11090956
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Involvement of Gtr1p in the oxidative stress response in yeast Saccharomyces cerevisiae.

    Sekiguchi, Takeshi / Ishii, Takashi / Kamada, Yoshiaki / Funakoshi, Minoru / Kobayashi, Hideki / Furuno, Nobuaki

    Biochemical and biophysical research communications

    2022  Volume 598, Page(s) 107–112

    Abstract: 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 ... ...

    Abstract 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 (H
    MeSH term(s) ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/metabolism ; Autophagy ; Gene Expression Regulation, Fungal ; Hydrogen Peroxide/pharmacology ; Monomeric GTP-Binding Proteins/genetics ; Monomeric GTP-Binding Proteins/metabolism ; Oxidative Stress/drug effects ; Oxidative Stress/physiology ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/physiology ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism
    Chemical Substances ATP-Binding Cassette Transporters ; Gtr1 protein, S cerevisiae ; SNQ2 protein, S cerevisiae ; Saccharomyces cerevisiae Proteins ; Hydrogen Peroxide (BBX060AN9V) ; Monomeric GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2022-02-08
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2022.02.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Prime-numbered Atg proteins act at the primary step in autophagy: unphosphorylatable Atg13 can induce autophagy without TOR inactivation.

    Kamada, Yoshiaki

    Autophagy

    2010  Volume 6, Issue 3, Page(s) 415–416

    Abstract: Autophagy is induced by inactivation of Tor complex 1 (TORC1), such as what happens during nutrient limitation and rapamycin treatment. However, the mechanism by which TORC1 regulates autophagy remains unclear. The Atg1 kinase complex that comprises Atg1 ...

    Abstract Autophagy is induced by inactivation of Tor complex 1 (TORC1), such as what happens during nutrient limitation and rapamycin treatment. However, the mechanism by which TORC1 regulates autophagy remains unclear. The Atg1 kinase complex that comprises Atg1 and its binding prime-numbered Atg proteins (Atg11, Atg13, Atg17, Atg29 and Atg31) has long been a candidate for TORC1's downstream target. This is especially the case for Atg13, a regulatory component of the Atg1 complex, which is highly phosphorylated in a TORC1-dependent manner. We find that yeast TORC1 directly phosphorylates Atg13 on at least eight Ser residues. Strikingly, expression of an unphosphorylatable Atg13 (Atg13- 8SA) mutant bypasses the TORC1 pathway to induce autophagy in vegetatively growing cells. Induction of autophagy by Atg13-8SA is accompanied by molecular events involving Atg proteins, such as formation of the Atg1 complex, activation of Atg1, and the organization of the pre-autophagosomal structure (PAS). These findings suggest that formation of the Atg1 complex is a primary step at induction of autophagy, and that dephosphorylation of Atg13 acts as a molecular switch to turn on starvation-induced autophagy.
    MeSH term(s) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Autophagy/physiology ; Autophagy-Related Proteins ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Humans ; Protein Kinases/genetics ; Protein Kinases/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Signal Transduction/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemical Substances ATG13 protein, S cerevisiae ; Adaptor Proteins, Signal Transducing ; Atg17 protein, S cerevisiae ; Atg31 protein, S cerevisiae ; Autophagy-Related Proteins ; CRTC1 protein, human ; Carrier Proteins ; Saccharomyces cerevisiae Proteins ; Transcription Factors ; Protein Kinases (EC 2.7.-) ; ATG1 protein, S cerevisiae (EC 2.7.1.-)
    Language English
    Publishing date 2010-04-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.4161/auto.6.3.11390
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  10. Article ; Online: Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis.

    Tai, Yen Teng / Fukuda, Tomoyuki / Morozumi, Yuichi / Hirai, Hayato / Oda, Arisa H / Kamada, Yoshiaki / Akikusa, Yutaka / Kanki, Tomotake / Ohta, Kunihiro / Shiozaki, Kazuhiro

    Molecular and cellular biology

    2023  Volume 43, Issue 12, Page(s) 675–692

    Abstract: Target of rapamycin complex 1 (TORC1) is activated in response to nutrient availability and growth factors, promoting cellular anabolism and proliferation. To explore the mechanism of TORC1-mediated proliferation control, we performed a genetic screen in ...

    Abstract Target of rapamycin complex 1 (TORC1) is activated in response to nutrient availability and growth factors, promoting cellular anabolism and proliferation. To explore the mechanism of TORC1-mediated proliferation control, we performed a genetic screen in fission yeast and identified Sfp1, a zinc-finger transcription factor, as a multicopy suppressor of temperature-sensitive TORC1 mutants. Our observations suggest that TORC1 phosphorylates Sfp1 and protects Sfp1 from proteasomal degradation. Transcription analysis revealed that Sfp1 positively regulates genes involved in ribosome production together with two additional transcription factors, Ifh1/Crf1 and Fhl1. Ifh1 physically interacts with Fhl1, and the nuclear localization of Ifh1 is regulated in response to nutrient levels in a manner dependent on TORC1 and Sfp1. Taken together, our data suggest that the transcriptional regulation of the genes involved in ribosome biosynthesis by Sfp1, Ifh1, and Fhl1 is one of the key pathways through which nutrient-activated TORC1 promotes cell proliferation.
    MeSH term(s) Transcription Factors/genetics ; Transcription Factors/metabolism ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Schizosaccharomyces/genetics ; Schizosaccharomyces/metabolism ; Mechanistic Target of Rapamycin Complex 1/metabolism ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Ribosomes/metabolism ; Cell Proliferation ; Gene Expression Regulation, Fungal
    Chemical Substances Transcription Factors ; Saccharomyces cerevisiae Proteins ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) ; DNA-Binding Proteins
    Language English
    Publishing date 2023-12-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1080/10985549.2023.2282349
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