Cited by 320Cancer, Lipids, and MetabolismFungal and yeast genetics researchLipid metabolism and biosynthesis

SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast.

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Hughes, Adam L., Todd, Bridget L., Espenshade, Peter J.·2005·Cell

Abstract

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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Crossref · 10.1016/j.cell.2005.01.012

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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
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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