SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast.
Open accessAbstract
Cholesterol and fatty acid synthesis in mammals are controlled by SREBPs, a family of membrane bound transcription factors. Our studies identified homologs of SREBP, its binding partner SCAP, and the ER retention protein Insig in Schizosaccharomyces pombe, named sre1+, scp1+, and ins1+. Like SREBP, Sre1 is cleaved and activated in response to sterol depletion in a Scp1-dependent manner. Microarray analysis revealed that Sre1 activates sterol biosynthetic enzymes as in mammals, and, surprisingly, Sre1 also stimulates transcription of genes required for adaptation to hypoxia. Furthermore, Sre1 rapidly activates these target genes in response to low oxygen and is itself required for anaerobic growth. Based on these findings, we propose and test a model in which Sre1 and Scp1 monitor oxygen-dependent sterol synthesis as an indirect measure of oxygen supply and mediate a hypoxic response in fission yeast.
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A novel mechanism of hypoxia adaptation mediated by sterol regulatory element-binding proteins (SREBPs) was characterized in Schizosaccharomyces pombe.
“Recently, a novel mechanism of hypoxia adaptation mediated by a highly conserved family of transcription factors, sterol regulatory element-binding proteins (SREBPs), was characterized in fission yeast, Schizosaccharomyces pombe [25].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [25]
AFUA_2g01260 (srbA) is induced 5.02 fold in response to hypoxia.
“only one, AFUA_2g01260 (induced 5.02 fold in response to hypoxia), had similarity with a functionally characterized protein, Sre1 from S. pombe [25]”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [25]
In the yeasts S. pombe and C. neoformans, SREBP homologs are crucial for sterol biosynthesis, survival under hypoxic conditions, resistance to azole antifungal agents, and fungal virulence.
“In the yeasts S. pombe and C. neoformans, SREBP homologs are crucial for sterol biosynthesis, survival under hypoxic conditions, resistance to azole antifungal agents, and fungal virulence [25],[32],[33].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [25]
C. neoformans lacks an apparent Insig homolog and the Insig homolog in S. pombe does not appear to be required for regulation of SREBP signalling.
“Interestingly, C. neoformans lacks an apparent Insig homolog and the Insig homolog in S. pombe does not appear to be required for regulation of SREBP signalling [25],[32].”
From A Sterol-Regulatory Element Binding Protein Is Required for Cell Polarity, Hypoxia Adaptation, Azole Drug Resistance, and Virulence in Aspergillus fumigatus (2008) · cites this paper as [25]
These transcriptional responses have been shown to be dependent on the presence of the azoles and/or depletion of ergosterol.
“To date, these transcriptional responses have been shown to be dependent on the presence of the azoles and/or depletion of ergosterol.”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Hughes et al., 2005
All above lines of evidence suggest that ergosterol depletion resulted from azole stress might be a cause for the transcriptional responses by ergosterol biosynthesis genes, but some direct experimental data in other fungi are still required for making a definite conclusion.
“All above lines of evidence suggest that ergosterol depletion resulted from azole stress might be a cause for the transcriptional responses by ergosterol biosynthesis genes, but some direct experimental data in other fungi are still required for making a definite conclusion.”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Hughes et al., 2005
Several lines of evidence suggest that ergosterol depletion might be a cause of azole-activated transcriptional responses by ergosterol biosynthesis genes.
“For azole-activated transcriptional responses by genes for ergosterol biosynthesis, several lines of evidence suggest that ergosterol depletion might be a cause.”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Hughes et al., 2005
In S. pombe, ergosterol depletion activated the expression of ergosterol biosynthesis genes and their regulator Sre1p.
“In Schizosaccharomyces pombe, it was reported that ergosterol depletion activated the expression of ergosterol biosynthesis genes and their regulator Sre1p (Hughes et al., 2005; Porter et al., 2010).”
From Abnormal Ergosterol Biosynthesis Activates Transcriptional Responses to Antifungal Azoles (2018) · cites this paper as Hughes et al., 2005
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References 44 · Cited by 320
- Authors
- Hughes, A. L., Todd, B. L., & Espenshade, P. J.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Espenshade, Peter J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 120
- Issue
- 6
- Pages
- 831-842
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2158645874
- Cited by
- 320
- References
- 44
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 10 · 2022: 6 · 2021: 15 · 2020: 14 · 2019: 12 · 2018: 10 · 2017: 21 · 2016: 17 · 2015: 21 · 2014: 12 · 2013: 14 · 2012: 15
- FWCI
- 7.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL077588, HL 077588)
- National Institute of General Medical Sciences (GM007445, T32GM007445)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Keywords
- SREBP, SCP1, Insig, sterol biosynthesis, oxygen sensing, hypoxia response, anaerobic growth, sterol depletion, transcriptional regulation, Schizosaccharomyces pombe, cholesterol biosynthesis, fatty acid synthesis
- MeSH terms
- Animals, Cholesterol, Cricetinae, Oxygen, Schizosaccharomyces, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, CHO Cells, Schizosaccharomyces pombe Proteins, Microarray Analysis
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