Ixr1p and the control of the Saccharomyces cerevisiae hypoxic response

Vizoso-Vázquez, Ángel; Lamas-Maceiras, Mónica; Becerra, Manuel; González-Siso, María-Isabel; Rodrı́guez-Belmonte, Esther; Cerdán, M. Esperanza

doi:10.1007/s00253-011-3785-2

Cited by 22 publications

(27 citation statements)

References 36 publications

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“…Loss of Ixr1 results in the transcriptional induction of many genes involved in cell metabolism and stress responses [ 35 ]. We considered the possibility that ixr1∆ weakly rescued TORC1-inhibited H3K37A cells indirectly due to transcriptional upregulation of normally Ixr1-repressed genes.…”

Section: Resultsmentioning

confidence: 99%

“…We considered the possibility that ixr1∆ weakly rescued TORC1-inhibited H3K37A cells indirectly due to transcriptional upregulation of normally Ixr1-repressed genes. We tested this by transforming H3WT and H3K37A cells with a control vector and, for H3K37A, individual galactose-inducible vectors expressing a subset of Ixr1-repressed genes linked to metabolism ( MET10 , PBI2 , GNA1 , and GID1 ) or stress responses ( STF2 , PAI3 , TIR1 , and TIR3 ) [ 35 ]. We also included a galactose-inducible YAP1 expression vector, since Yap1 induces stress response genes [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

“…These results also demonstrate that the necrosis induced by TORC1 inhibition in H3K37A cells is caused by impaired vacuole homeostasis and pH dysregulation. The ability of ixr1∆ to weakly rescue H3K37A is therefore most likely indirectly caused by the increased expression of acid stress response genes such as TIR1 [ 35 ].

Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms driving these differences are not immediately obvious but could be related to the distinct functions of each HMGB. For example, Ixr1 has a potential role as a stress response regulator since it functions both as a transcriptional activator and as repressor of many target genes involved in this process [ 35 ]. Since TORC1 inhibition activates the environmental stress response, TORC1 repression may restore Ixr1 nuclear localization in H3K37A by overriding the inhibitory effect H3K37A has on Ixr1 chromatin binding [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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Histone H3 and TORC1 prevent organelle dysfunction and cell death by promoting nuclear retention of HMGB proteins

Chen

Workman

Strahl

et al. 2016

Epigenetics & Chromatin

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BackgroundHow cells respond and adapt to environmental changes, such as nutrient flux, remains poorly understood. Evolutionarily conserved nutrient signaling cascades can regulate chromatin to contribute to genome regulation and cell adaptation, yet how they do so is only now beginning to be elucidated. In this study, we provide evidence in yeast that the conserved nutrient regulated target of rapamycin complex 1 (TORC1) pathway, and the histone H3N-terminus at lysine 37 (H3K37), function collaboratively to restrict specific chromatin-binding high mobility group box (HMGB) proteins to the nucleus to maintain cellular homeostasis and viability.ResultsReducing TORC1 activity in an H3K37 mutant causes cytoplasmic localization of the HMGB Nhp6a, organelle dysfunction, and both non-traditional apoptosis and necrosis. Surprisingly, under nutrient-rich conditions the H3K37 mutation increases basal TORC1 signaling. This effect is prevented by individual deletion of the genes encoding HMGBs whose cytoplasmic localization increases when TORC1 activity is repressed. This increased TORC1 signaling also can be replicated in cells by overexpressing the same HMGBs, thus demonstrating a direct and unexpected role for HMGBs in modulating TORC1 activity. The physiological consequence of impaired HMGB nuclear localization is an increased dependence on TORC1 signaling to maintain viability, an effect that ultimately reduces the chronological longevity of H3K37 mutant cells under limiting nutrient conditions.ConclusionsTORC1 and histone H3 collaborate to retain HMGBs within the nucleus to maintain cell homeostasis and promote longevity. As TORC1, HMGBs, and H3 are evolutionarily conserved, our study suggests that functional interactions between the TORC1 pathway and histone H3 in metazoans may play a similar role in the maintenance of homeostasis and aging regulation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13072-016-0083-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Histone H3 and TORC1 prevent organelle dysfunction and cell death by promoting nuclear retention of HMGB proteins

Chen

Workman

Strahl

et al. 2016

Epigenetics & Chromatin

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“…Ixr1 also regulates other hypoxic genes like TIR1, a cell wall mannoprotein of the serine-alanine-rich protein family [65] and HEM13, which encodes the enzyme coproporphyrinogen III oxidase in the heme biosynthetic pathway [66]. The whole set of genes that are regulated by Ixr1 during the hypoxic response was determined in a genome-wide approach [67]. Hypoxic genes are also regulated by oxidative stress.…”

Section: Direct Binding To Target Promotersmentioning

confidence: 99%

HMGB Proteins from Yeast to Human. Gene Regulation, DNA Repair and Beyond

Vizoso-Vázquez¹,

Barreiro-Alonso²,

Rico-Díaz³

et al. 2017

Old Yeasts - New Questions

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HMGB proteins are characterized for containing one or more HMG-box domains and are well conserved from yeasts to higher eukaryotes. The HMG-box domain is formed by three α-helices with an L-shaped fold. Although HMGB proteins also have cytoplasmic and extracellular functions, they bind to nuclear or mitochondrial DNA in a highly dynamic process that affects chromatin organization. In this review, we mainly focus on HMGB proteins from yeast and their human homologs as functionally involved in DNA repair and transcriptional regulation. Recent research reveals that these proteins participate in epigenetic control of gene expression, aging, disease, or stem-cell biology.

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An overview of branched-chain amino acid aminotransferases: functional differences between mitochondrial and cytosolic isozymes in yeast and human

Toyokawa

Koonthongkaew

Takagi

2021

Appl Microbiol Biotechnol

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Branched-chain amino acid aminotransferase (BCAT) catalyzes bidirectional transamination in the cell between branchedchain amino acids (BCAAs; valine, leucine, and isoleucine) and branched-chain α-keto acids (BCKAs; α-ketoisovalerate, α-ketoisocaproate, and α-keto-β-methylvalerate). Eukaryotic cells contain two types of paralogous BCATs: mitochondrial BCAT (BCATm) and cytosolic BCAT (BCATc). Both isozymes have identical enzymatic functions, so they have long been considered to perform similar physiological functions in the cells. However, many studies have gradually revealed the differences in physiological functions and regulatory mechanisms between them. In this article, we present overviews of BCATm and BCATc in both yeast and human. We also introduce BCAT variants found natively or constructed artificially, which could have significant implications for research into the relationship between the primary structures and protein functions of BCATs. Key points • BCAT catalyzes bidirectional transamination in the cell betweenBCAAs and BCKAs. • BCATm and BCATc are different in the metabolic roles and regulatory mechanisms. • BCAT variants offer insight into a relationship between the structure and function. Keywords Branched-chain amino acid aminotransferase • Branched-chain amino acid • Branched-chain α-keto acid • Yeast • Saccharomyces cerevisiae

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Ixr1p and the control of the Saccharomyces cerevisiae hypoxic response

Cited by 22 publications

References 36 publications

Histone H3 and TORC1 prevent organelle dysfunction and cell death by promoting nuclear retention of HMGB proteins

Histone H3 and TORC1 prevent organelle dysfunction and cell death by promoting nuclear retention of HMGB proteins

HMGB Proteins from Yeast to Human. Gene Regulation, DNA Repair and Beyond

An overview of branched-chain amino acid aminotransferases: functional differences between mitochondrial and cytosolic isozymes in yeast and human

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