SEA and GATOR 10 Years Later

Loissell-Baltazar, Yahir A.; Dokudovskaya, Svetlana

doi:10.3390/cells10102689

Cited by 10 publications

(4 citation statements)

References 212 publications

(385 reference statements)

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“…One of the major upstream regulators of the mTORC1 pathway, the GATOR1 complex, is involved in the regulation of nutrient sensing and responding. Various mutations of the genes encoding GATOR1 proteins have been detected in many solid tumors [ 73 ]. Notably, a low expression of NPRL2, one of the GATOR1 components, in different types of lung cancers is correlated with cisplatin resistance [ 74 , 75 ].…”

Section: Mtorc1 Pathway and Cisplatin Resistancementioning

confidence: 99%

The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics

Pan

Zhang

Dokudovskaya

2023

IJMS

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Cisplatin (cis-diamminedichloroplatinum I) is a platinum-based drug, the mainstay of anticancer treatment for numerous solid tumors. Since its approval by the FDA in 1978, the drug has continued to be used for the treatment of half of epithelial cancers. However, resistance to cisplatin represents a major obstacle during anticancer therapy. Here, we review recent findings on how the mTORC1 pathway and autophagy can influence cisplatin sensitivity and resistance and how these data can be applicable for the development of new therapeutic strategies.

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Section: Mtorc1 Pathway and Cisplatin Resistancementioning

confidence: 99%

The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics

Pan

Zhang

Dokudovskaya

2023

IJMS

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“…, 2011 ; Bar-Peled et al. , 2013 ; Loissell-Baltazar and Dokudovskaya, 2021 ; Valenstein et al. , 2022 ).…”

Section: Examples Of Coatomer Neofunctionalizationunclassified

Coatomer in the universe of cellular complexity

Field

Rout

2022

MBoC

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Eukaryotic cells possess considerable internal complexity, differentiating them from prokaryotes. Eukaryogenesis, an evolutionary transitional period culminating in the last eukaryotic common ancestor (LECA), marked the origin of the eukaryotic endomembrane system. LECA is reconstructed as possessing intracellular complexity akin to modern eukaryotes. Construction of endomembrane compartments involved three key gene families: coatomer, BAR-domain proteins, and ESCRT. Each has a distinct evolutionary origin, but of these coatomer and BAR proteins are eukaryote specific, while ESCRT has more ancient origins. We discuss the structural motifs defining these three membrane-coating complexes and suggest that compared with BAR and ESCRT, the coatomer architecture had a unique ability to be readily and considerably modified, unlocking functional diversity and enabling the development of the eukaryotic cell.

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“…The SEh1-Associated protein 4 is part of the SEACAT (SEA subcomplex activating TORC1) that is an upstream regulator of TORC1 (Target of Rapamycin Complex 1) pathway, involved in various cellular activities, such as cell growth, ribosome biogenesis, translation initiation, metabolism, stress response, aging, and autophagy (Inoue and Nomura 2018). TORC1 integrates signals from a wide variety of intracellular and extracellular cues to maintain optimal growth and metabolism (Dokudovskaya and Rout 2015;Loissell-Baltazar and Dokudovskaya 2021) and has been reported to sense and respond to oxidative stress in a complex manner (Su and Dai 2017). Furthermore, PKC1 is a direct substrate of TORC2 (Nomura and Inoue 2015)( -another complex of the TOR kinase -that is also activated in response to oxidative stress in S. cerevisiae (Niles and Powers 2014).…”

Section: Understanding the Genetic Basis Of Complex Traits Related To Industrialmentioning

confidence: 99%

Genetic mapping of a bioethanol yeast strain reveals new targets for aldehyde- and thermotolerance

Mello

Coradini

Carazzolle

et al. 2021

Preprint

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Current technology that enables bioethanol production from agricultural biomass imposes harsh conditions for Saccharomyces cerevisiae’s metabolism. In this work, the genetic architecture of industrial bioethanol yeast strain SA-1 was evaluated. SA-1 segregant FMY097 was previously described as highly aldehyde resistant and here also as thermotolerant: two important traits for the second-generation industry. A Quantitative Trait Loci (QTL) mapping of 5-hydroxymethylfurfural (HMF) -resistant segregants of hybrid FMY097/BY4742 disclosed a region in chromosome II bearing alleles with uncommon non-synonymous (NS) single nucleotide polymorphisms (SNPs) in FMY097: MIX23, PKC1, SEA4, and SRO77. Allele swap to susceptible laboratory strain BY4742 revealed that SEA4FMY097 enhances robustness towards HMF, but the industrial fitness could not be fully recovered. The genetic network arising from the causative genes in the QTL window suggests that intracellular signaling TOR (Target of Rapamycin) and CWI (Cell Wall Integrity) pathways are regulators of this phenotype in FMY097. Because the QTL mapping did not result in one major allelic contribution to the evaluated trait, a background effect in FMY097’s HMF resistance is expected. Quantification of NADPH - cofactor implied in endogenous aldehyde detoxification reactions - supports the former hypothesis, given its high availability in FMY097. Regarding thermotolerance, SEA4FMY097 grants BY4742 ability to grow in temperatures as high as 38 °C in liquid, while allele PKC1FMY097 allows growth up to 40 °C in solid medium. Both SEA4FMY097 and PKC1FMY097 encode rare NS SNPs, not found in other >1,013 S. cerevisiae. Altogether, these findings point towards crucial membrane and stress mediators for yeast robustness.KEY POINTSQTL mapping of the HMF-resistant strain FMY097 reveals a region enriched with SNPs in Chr IISEA4FMY097 has rare non-synonymous mutations and improves cell growth at 10 mM HMF and 38°CPKC1FMY097 has rare non-synonymous mutations and improves cell growth at 40 °C in solid media

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SEA and GATOR 10 Years Later

Cited by 10 publications

References 212 publications

The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics

The Role of mTORC1 Pathway and Autophagy in Resistance to Platinum-Based Chemotherapeutics

Coatomer in the universe of cellular complexity

Genetic mapping of a bioethanol yeast strain reveals new targets for aldehyde- and thermotolerance

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