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Reference - PMID:39910760 - Novel TORC1 inhibitor Ecl1 is regulated by phosphorylation in fission yeast.

Reference summary

PubMed ID
PMID:39910760
Title
Novel TORC1 inhibitor Ecl1 is regulated by phosphorylation in fission yeast.
Authors
Ohtsuka H, Kawai S, Ito Y, Kato Y, Shimasaki T, Imada K, Otsubo Y, Yamashita A, Mishiro-Sato E, Kuwata K, Aiba H
Citation
Aging Cell 2025 Feb 05;:e14450
Publication year
2025
Abstract
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.

Annotation

GO biological process

GO:1904262 - negative regulation of TORC1 signaling

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GO cellular component

GO:0005737 - cytoplasm

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GO:0005634 - nucleus

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GO molecular function

GO:0030291 - protein serine/threonine kinase inhibitor activity

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Modification

MOD:00046 - O-phospho-L-serine

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MOD:00047 - O-phospho-L-threonine

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Multi-locus phenotype

FYPO:0001838 - decreased protein phosphorylation during vegetative growth

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FYPO:0001309 - increased viability in stationary phase

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FYPO:0000280 - sterile

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Single locus phenotype

FYPO:0005097 - abnormal cell cycle arrest in mitotic G1 phase

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FYPO:0000708 - decreased mating efficiency

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FYPO:0004085 - decreased vegetative cell growth

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FYPO:0001309 - increased viability in stationary phase

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FYPO:0000644 - normal protein localization during vegetative growth

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FYPO:0000776 - normal protein phosphorylation during vegetative growth

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FYPO:0000703 - normal protein-protein interaction

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FYPO:0000280 - sterile

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