Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation

Clasen, Sara J; Shao, Wei; He, Gu; Espenshade, Peter J.

doi:10.7554/elife.28563

Cited by 7 publications

(4 citation statements)

References 50 publications

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“…Since casein kinase 1 family member Hhp2 accelerates Sre1N degradation, our results suggested that Ssp2/Gsk3/Gsk31 might act as inhibitors of Hhp2, or alternatively act on Sre1N activity independently of Hhp2. Previous studies suggested that Sre1 cleavage, Sre1N stability and Sre1N DNA binding are involved in the regulation of Sre1 activity [30][31][32]. Based on our present results, we propose that Ssp2 and Gsk3/Gsk31 might affect Sre1N stability to regulate Sre1 activity.…”

Section: Discussionsupporting

confidence: 76%

AMPKα Subunit Ssp2 and Glycogen Synthase Kinases Gsk3/Gsk31 are involved in regulation of sterol regulatory element-binding protein (SREBP) activity in fission yeast

et al. 2020

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Sterol regulatory element-binding protein (SREBP), a highly conserved family of membrane-bound transcription factors, is an essential regulator for cellular cholesterol and lipid homeostasis in mammalian cells. Sre1, the homolog of SREBP in the fission yeast Schizosaccharomyces pombe (S. pombe), regulates genes involved in the transcriptional responses to low sterol as well as low oxygen. Previous study reported that casein kinase 1 family member Hhp2 phosphorylated the Sre1 N-terminal transcriptional factor domain (Sre1N) and accelerated Sre1N degradation, and other kinases might exist for regulating the Sre1 function. To gain insight into the mechanisms underlying the Sre1 activity and to identify additional kinases involved in regulation of Sre1 function, we developed a luciferase reporter system to monitor the Sre1 activity through its binding site called SRE2 in living yeast cells. Here we showed that both ergosterol biosynthesis inhibitors and hypoxia-mimic CoCl 2 caused a dose-dependent increase in the Sre1 transcription activity, concurrently, these induced transcription activities were almost abolished in Δsre1 cells. Surprisingly, either AMPKα Subunit Ssp2 deletion or Glycogen Synthase Kinases Gsk3/Gsk31 double deletion significantly suppressed ergosterol biosynthesis inhibitors-or CoCl 2-induced Sre1 activity. Notably, the Δssp2Δgsk3Δgsk31 mutant showed further decreased Sre1 activity when compared with their single or double deletion. Consistently, the Δssp2Δgsk3Δgsk31 mutant showed more marked temperature sensitivity than any of their single or double deletion. Moreover, the fluorescence of GFP-Sre1N localized at the nucleus in wild-type cells, but significantly weaker nuclear fluorescence of GFP-Sre1N was observed in Δssp2, Δgsk3Δgsk31, Δssp2Δgsk3, Δssp2Δgsk31 or Δssp2Δgsk3Δgsk31 cells. On the other hand, the immunoblot showed a dramatic decrease in GST-Sre1N levels in the Δgsk3Δgsk31 or the Δssp2Δgsk3Δgsk31 cells but not in the Δssp2 cells. Altogether, our findings suggest that Gsk3/Gsk31 may regulate Sre1N degradation, while Ssp2 may regulate not only the degradation of Sre1N but also its translocation to the nucleus.

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Section: Discussionsupporting

confidence: 76%

AMPKα Subunit Ssp2 and Glycogen Synthase Kinases Gsk3/Gsk31 are involved in regulation of sterol regulatory element-binding protein (SREBP) activity in fission yeast

et al. 2020

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“…In contrast to ZmAKR4C9 , ZmRPS23 belongs to the ribosomal protein S12/S23 family that functions in translation fidelity [103]. Interestingly, several studies identified RPS23 as an enzyme substrate for the oxygenase OFD1 in fission yeast [104]. When little oxygen is around, OFD1 cannot hydroxylate RPS23.…”

Section: Discussionmentioning

confidence: 99%

A systems biology approach uncovers a gene co-expression network associated with cell wall degradability in maize

et al. 2019

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Understanding the mechanisms triggering variation of cell wall degradability is a prerequisite to improving the energy value of lignocellulosic biomass for animal feed or biorefinery. Here, we implemented a multiscale systems approach to shed light on the genetic basis of cell wall degradability in maize. We demonstrated that allele replacement in two pairs of near-isogenic lines at a region encompassing a major quantitative trait locus (QTL) for cell wall degradability led to phenotypic variation of a similar magnitude and sign to that expected from a QTL analysis of cell wall degradability in the F271 × F288 recombinant inbred line progeny. Using DNA sequences within the QTL interval of both F271 and F288 inbred lines and Illumina RNA sequencing datasets from internodes of the selected near-isogenic lines, we annotated the genes present in the QTL interval and provided evidence that allelic variation at the introgressed QTL region gives rise to coordinated changes in gene expression. The identification of a gene co-expression network associated with cell wall-related trait variation revealed that the favorable F288 alleles exploit biological processes related to oxidation-reduction, regulation of hydrogen peroxide metabolism, protein folding and hormone responses. Nested in modules of co-expressed genes, potential new cell-wall regulators were identified, including two transcription factors of the group VII ethylene response factor family, that could be exploited to fine-tune cell wall degradability. Overall, these findings provide new insights into the regulatory mechanisms by which a major locus influences cell wall degradability, paving the way for its map-based cloning in maize.

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“…Both low oxygen and physiological CO 2 promote the stability of Ume6, allowing filamentation to proceed (84). PHD-mediated regulation of the sterol regulatory element binding protein (SREBP)-mediated low-oxygen response through Ofd1 homologs is well studied in fission yeast, but its overall role in fungal pathogenesis remains ill-defined despite Ofd1 homologs being present in many human-pathogenic fungi (25,66,79).…”

Section: Oxygen and Fungal Disease Progression: Fungal Morphogenesis ...mentioning

confidence: 99%

Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression

Puerner,

Vellanki,

Strauch

et al. 2023

Annu. Rev. Microbiol.

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Fungal-mediated disease progression and antifungal drug efficacy are significantly impacted by the dynamic infection microenvironment. At the site of infection, oxygen often becomes limiting and induces a hypoxia response in both the fungal pathogen and host cells. The fungal hypoxia response impacts several important aspects of fungal biology that contribute to pathogenesis, virulence, antifungal drug susceptibility, and ultimately infection outcomes. In this review, we summarize recent advances in understanding the molecular mechanisms of the hypoxia response in the most common human fungal pathogens, discuss potential therapeutic opportunities, and highlight important areas for future research.

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Prolyl dihydroxylation of unassembled uS12/Rps23 regulates fungal hypoxic adaptation

Cited by 7 publications

References 50 publications

AMPKα Subunit Ssp2 and Glycogen Synthase Kinases Gsk3/Gsk31 are involved in regulation of sterol regulatory element-binding protein (SREBP) activity in fission yeast

AMPKα Subunit Ssp2 and Glycogen Synthase Kinases Gsk3/Gsk31 are involved in regulation of sterol regulatory element-binding protein (SREBP) activity in fission yeast

A systems biology approach uncovers a gene co-expression network associated with cell wall degradability in maize

Recent Advances in Understanding the Human Fungal Pathogen Hypoxia Response in Disease Progression

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