mTOR-S6K1 pathway mediates cytoophidium assembly

Sun, Zhe; Liu, Ji‐Long

doi:10.1016/j.jgg.2018.11.006

Cited by 44 publications

(34 citation statements)

References 51 publications

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“…1, D and E ). In agreement with our data, it has been demonstrated that rapamycin only mildly reduces the growth rate in fission yeast cells, whereas TORC1 activation is significantly inhibited (56–58), as is in mammalian cells treated with rapamycin (51).…”

Section: Resultssupporting

confidence: 92%

“…Drug inhibition of TOR signaling has been shown to reduce cytoophidium formation in mammalian cells (51). To test whether the same is true for fission yeast, we utilized everolimus and rapamycin, two well-established allosteric inhibitors of TORC1 pathway.…”

Section: Resultsmentioning

confidence: 99%

“…In mammalian systems, it has been shown that CTPS filamentation is mediated by mTORC1–S6K1-signaling pathway (51). Along with establishing the effects of the absence of single TORC1 and TORC2 subunits on Cts1 filaments in S. pombe , we explored whether the TOR downstream regulatory phosphorylation cascade system and/or other downstream effectors could mediate the formation of cytoophidia in fission yeast.…”

Section: Resultsmentioning

confidence: 99%

“…We have recently shown that the mTORC1–S6K1 pathway mediates cytoophidium assembly in mammalian cells and that mTOR is required for cytoophidium assembly in Drosophila (51). Here, we tested the universality of this type of regulation in lower eukaryotes, using the unicellular eukaryotic organism S. pombe .…”

Section: Introductionmentioning

confidence: 99%

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The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe

Andreadis

Hulme

Wensley

et al. 2019

Journal of Biological Chemistry

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CTP synthase (CTPS) has been demonstrated to form evolutionarily-conserved filamentous structures termed cytoophidia whose exact cellular functions remain unclear, but they may play a role in intracellular compartmentalization. We have previously shown that the mammalian target of rapamycin complex 1 (mTORC1)–S6K1 pathway mediates cytoophidium assembly in mammalian cells. Here, using the fission yeast Schizosaccharomyces pombe as a model of a unicellular eukaryote, we demonstrate that the target of rapamycin (TOR)-signaling pathway regulates cytoophidium formation (from the S. pombe CTPS ortholog Cts1) also in S. pombe. Conducting a systematic analysis of all viable single TOR subunit–knockout mutants and of several major downstream effector proteins, we found that Cts1 cytoophidia are significantly shortened and often dissociate when TOR is defective. We also found that the activities of the downstream effector kinases of the TORC1 pathway, Sck1, Sck2, and Psk1 S6, as well as of the S6K/AGC kinase Gad8, the major downstream effector kinase of the TORC2 pathway, are necessary for proper cytoophidium filament formation. Interestingly, we observed that the Crf1 transcriptional corepressor for ribosomal genes is a strong effector of Cts1 filamentation. Our findings connect TOR signaling, a major pathway required for cell growth, with the compartmentalization of the essential nucleotide synthesis enzyme CTPS, and we uncover differences in the regulation of its filamentation among higher multicellular and unicellular eukaryotic systems.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe

Andreadis

Hulme

Wensley

et al. 2019

Journal of Biological Chemistry

Self Cite

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“…mTOR has also been implicated in CTPS filament formation in Drosophila ( Aughey et al. , 2014 ; Sun and Liu, 2019 ). In Drosophila ovaries, CTPS filament assembly is regulated by Myc and activated cdc42-associated kinase (Ack; Strochlic et al.…”

Section: Introductionmentioning

confidence: 99%

Freedom of assembly: metabolic enzymes come together

Simonet

Burrell

Kollman

et al. 2020

MBoC

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Many different enzymes in intermediate metabolism dynamically assemble filamentous polymers in cells, often in response to changes in physiological conditions. Most of the enzyme filaments known to date have only been observed in cells, but in a handful of cases structural and biochemical studies have revealed the mechanisms and consequences of assembly. In general, enzyme polymerization functions as a mechanism to allosterically tune enzyme kinetics, and it may play a physiological role in integrating metabolic signaling. Here, we highlight some principles of metabolic filaments by focusing on two well-studied examples in nucleotide biosynthesis pathways—inosine-5’-monophosphate (IMP) dehydrogenase and cytosine triphosphate (CTP) synthase.

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Retracted: Britannin mediates apoptosis and glycolysis of T‐cell lymphoblastic lymphoma cells by AMPK‐dependent autophagy

Hong

Luo

Xie

et al. 2022

J Biochem & Molecular Tox

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The above article, published online on 19 September 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/abs/10.1002/jbt.23211), has been retracted by agreement between the authors, the journal Editor in Chief, Hari Bhat, and Wiley Periodicals, LLC.The article is being retracted at the authors' request because some of the data underlying this article refer to a different cell line from the one reported in it. As a result, the article's conclusions do not accurately reflect the full data and cannot be considered reliable.

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mTOR-S6K1 pathway mediates cytoophidium assembly

Cited by 44 publications

References 51 publications

The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe

The TOR pathway modulates cytoophidium formation in Schizosaccharomyces pombe

Freedom of assembly: metabolic enzymes come together

Retracted: Britannin mediates apoptosis and glycolysis of T‐cell lymphoblastic lymphoma cells by AMPK‐dependent autophagy

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