Publications by authors named "Takashi Ushimaru"

Endosomal sorting complex required for transport (ESCRT) is required for maintenance of nuclear functions and prevention of neurodegenerative diseases. The budding yeast Saccharomyces cerevisiae is an ideal model for studying ESCRT-dependent diseases. Nucleolar proteins are degraded by macronucleophagy and micronucleophagy after nutrient depletion and inactivation of target of rapamycin complex 1 (TORC1) kinase.

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Article Synopsis
  • * Micronucleophagy occurs at the nucleus-vacuole junction (NVJ), where a section of the nucleus, containing nucleolar proteins, is pushed into the vacuole for degradation after the protein kinase TORC1 is inactivated due to nutrient starvation.
  • * The study found that VAMP-associated proteins (VAPs), specifically Scs2 and Scs22, are essential for maintaining the integrity of the NVJ and facilitating the degradation process, highlighting their significant role in
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Vacuoles and lysosomes are organelles involved in the degradation of cytoplasmic proteins and organelles. Vacuolar morphology is dynamically regulated by fission and fusion in budding yeast. Vacuolar fusion is elicited in nutrient-depleted conditions and mediated by inactivation of target of rapamycin complex 1 (TORC1) protein kinase.

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When asynchronously growing cells suffer from nutrient depletion and inactivation of target of rapamycin complex 1 (TORC1) protein kinase, the rDNA (rRNA gene) region is condensed in budding yeast Saccharomyces cerevisiae, which is executed by condensin and Cdc14 protein phosphatase. However, it is unknown whether these mitotic factors can condense the rDNA region in nutrient-starved interphase cells. Here, we show that condensin is not involved in TORC1 inactivation-induced rDNA condensation in G1 cells.

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Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells.

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Article Synopsis
  • Phosphatidylinositol 3-phosphate (PI3P) is an important molecule generated by specific enzymes (PI3K complex I and II) that plays roles in cellular processes like macroautophagy and microautophagy, especially during nutrient stress.
  • PI3K complex I is needed for macroautophagy, while PI3K complex II is crucial for microautophagy, particularly in the recruitment of the ESCRT complex which aids in the formation of vesicles in cells.
  • The study highlights that PI3KCII and its product PI3P are essential for activating microautophagy in nutrient-stressed cells through the recruitment of Vps27 to vacuolar membranes, ultimately contributing to
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Remodeling of vacuolar membranes mediated by endosomal sorting complex required for transport (ESCRT) is critical for microautophagy induction in budding yeast. Nutrient depletion and inactivation of target of rapamycin complex 1 (TORC1) protein kinase elicit recruitment of the ESCRT-0 complex (Vps27-Hse1) onto vacuolar membranes and ESCRT-mediated microautophagy induction. Mitotic protein phosphatase Cdc14 antagonizes TORC1-mediated phosphorylation in macroautophagy induction after nutrient starvation and TORC1 inactivation.

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The degradation of nucleolar proteins - nucleophagy - is elicited by nutrient starvation or the inactivation of target of rapamycin complex 1 (TORC1) protein kinase in budding yeast. Prior to nucleophagy, nucleolar proteins migrate to the nucleus-vacuole junction (NVJ), where micronucleophagy occurs, whereas rDNA (rRNA gene) repeat regions are condensed and escape towards NVJ-distal sites. This suggests that the NVJ controls nucleolar dynamics from outside of the nucleus after TORC1 inactivation, but its molecular mechanism is unclear.

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Chromosomes have their own territories and dynamically translocate in response to internal and external cues. However, whether and how territories and the relocation of chromosomes are controlled by other intracellular organelles remains unknown. Upon nutrient starvation and target of rapamycin complex 1 (TORC1) inactivation, micronucleophagy, which preferentially degrades nucleolar proteins, occurs at the nucleus-vacuole junction (NVJ) in budding yeast.

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Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase elicits nucleophagy degrading nucleolar proteins in budding yeast. After TORC1 inactivation, nucleolar proteins are relocated to sites proximal to the nucleus-vacuole junction (NVJ), where micronucleophagy occurs, whereas ribosomal DNA (rDNA encoding rRNA) escapes from the NVJ. Condensin-mediated rDNA condensation promotes the repositioning and nucleophagic degradation of nucleolar proteins.

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Article Synopsis
  • Microautophagy is a process that breaks down cellular components during nutrient scarcity and is influenced by the inactivation of the TORC1 protein.
  • Previous studies using Vph1-GFP to assess microautophagy suggested that the ESCRT system was essential for this process; however, it was found that Vph1-GFP accumulation in ESCRT mutants did not accurately reflect ESCRT's role.
  • The study demonstrates that, despite some proteins reaching vacuolar membranes correctly in ESCRT-deficient cells, the necessary degradation of certain tagged proteins like GFP-Pho8 and Sna4-GFP still relies on ESCRT during nutrient deprivation, confirming ESCRT's vital role in microautophagy.
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The yeast E2F functional homologs MBF (Mbp1/Swi6) and SBF (Swi4/Swi6) complexes are critical transcription factors for G1/S transition. The target of rapamycin complex 1 (TORC1) kinase promotes G1/S transition via upregulation of the G1 cyclin Cln3 that activates MBF and SBF in favorable nutrient conditions. Here, we show evidence that TORC1 directly regulates G1/S transition via MBF and SBF.

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Deformation of vacuolar membranes mediated by endosomal sorting complex required for transport (ESCRT) is necessary for microautophagy. Target of rapamycin complex 1 (TORC1) protein kinase negatively regulates ESCRT-0 (Vps27-Hse1) recruitment onto vacuolar membranes and microautophagy induction. However, whether and how protein phosphatase regulates these events is unknown.

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The target of rapamycin complex 1 (TORC1) protein kinase is activated by nutrients and controls nutrient uptake via the membrane trafficking of various nutrient permeases. However, its molecular mechanisms remain elusive. Cholesterol (ergosterol in yeast) in conjunction with sphingolipids forms tight-packing microdomains, "lipid rafts", which are critical for intracellular protein sorting.

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Microautophagy is promoted after nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) kinase. Invagination of vacuolar membranes by endosomal sorting complex required for transport (ESCRT) is required for microautophagy. Vps27, a subunit of ESCRT-0, is recruited onto vacuolar membranes via dephosphorylation after TORC1 inactivation.

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Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase induce nucleophagy preferentially degrading only nucleolar components in budding yeast. Nucleolar proteins are relocated to sites proximal to the nucleus-vacuole junction (NVJ), where micronucleophagy occurs, whereas rDNA, which is embedded in the nucleolus under normal conditions, moves to NVJ-distal regions, causing rDNA dissociation from nucleolar proteins after TORC1 inactivation. This repositioning is mediated via chromosome linkage INM protein (CLIP)-cohibin complexes that tether rDNA to the inner nuclear membrane.

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Nucleolar proteins such as Nop1/fibrillarin are degraded by nucleophagy in nutrient-starved conditions. However, whether and how excess nucleolar proteins are removed in normal conditions is unknown. Here we show that overexpressed nucleolar protein Nop1 is toxic and degraded in nutrient-rich conditions in budding yeast.

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Target of rapamycin complex 1 (TORC1) protein kinase responds to various stresses including genotoxic stress. However, its molecular mechanism is poorly understood. Here, we show that DNA damage induces nonselective and selective autophagy in budding yeast.

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Misfolded and aggregated proteins are eliminated to maintain protein homeostasis. Autophagy contributes to the removal of protein aggregates. However, if and how proteotoxic stress induces autophagy is poorly understood.

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Target of rapamycin complex 1 (TORC1) protein kinase, a master controller of cell growth, is thought to be involved in genome integrity. However, the molecular mechanisms associated with this are unclear. Here, we show that TORC1 inactivation causes decreases in the levels of a wide range of proteins involved in the DNA damage checkpoint (DDC) signaling including Tel1, Mre11, Rad9, Mrc1, and Chk1 in budding yeast.

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Cdh1, a substrate-recognition subunit of anaphase-promoting complex/cyclosome (APC/C), is a tumor suppressor, and it is downregulated in various tumor cells in humans. APC/C-Cdh1 is activated from late M phase to G1 phase by antagonizing Cdk1-mediated inhibitory phosphorylation. However, how Cdh1 protein levels are properly regulated is ill-defined.

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Accurate regulation of activity and level of the MCM complex is critical for precise DNA replication and genome transmission. Cyclin-dependent kinase (CDK) negatively regulates nuclear localization of the MCM complex via phosphorylation of the Mcm3 subunit. More recently, we found that Mcm3 is degraded via the Skp1-Cullin-F-box (SCF)-proteasome axis in budding yeast.

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Accurate DNA replication is at the heart of faithful genome transmission in dividing cells. DNA replication is strictly controlled by various factors. However, how environmental stresses such as nutrient starvation impact on these factors and DNA replication is largely unknown.

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Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase promotes macroautophagy. Macroautophagy is a lipid-consuming process, and Nem1/Spo7 protein phosphatase and Pah1/lipin phosphatidate phosphatase are activated after TORC1 inactivation, supporting macroautophagy induction in the budding yeast Saccharomyces cerevisiae. On the other hand, whether and how microautophagy, which also consumes lipids, is regulated by TORC1 is controversial.

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Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites.

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