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The SREBP Pathway in Drosophila
Open accessAbstract
In mammals, synthesis of cholesterol and unsaturated fatty acids is controlled by SREBPs, a family of membrane-bound transcription factors. Here, we show that the Drosophila genome encodes all components of the SREBP pathway, including a single SREBP (dSREBP), SREBP cleavage-activating protein (dSCAP), and the two proteases that process SREBP at sites 1 and 2 to release the nuclear fragment. In cultured Drosophila S2 cells, dSREBP is processed at sites 1 and 2, and the liberated fragment increases mRNAs encoding enzymes of fatty acid biosynthesis, but not sterol or isoprenoid biosynthesis. Processing requires dSCAP, but is not inhibited by sterols as in mammals. Instead, dSREBP processing is blocked by palmitic acid. These findings suggest that the ancestral SREBP pathway functions to maintain membrane integrity rather than to control cholesterol homeostasis.
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“It has been previously shown that the homologs of SREBPs do not respond to changes in cholesterol, but rather changes in palmitate and/or phospholipids (39,40).”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [40]
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“D. melanogaster is a cholesterol auxotroph and activation of SREBP is regulated by reduced levels of palmitate and/or phospholipids.”
From Expression of miR-33 from an SREBP2 Intron Inhibits Cholesterol Export and Fatty Acid Oxidation* (2010) · cites this paper as [40]
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Metadata
- Authors
- Seegmiller, A. C., Dobrosotskaya, I., Goldstein, J. L., Ho, Y. K., Brown, M. S., & Rawson, R. B.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Goldstein, Joseph L.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 2
- Issue
- 2
- Pages
- 229-238
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W1993125269
- Cited by
- 194
- References
- 45
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 12 · 2023: 10 · 2022: 8 · 2021: 3 · 2020: 11 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 3 · 2015: 11 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 6.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- National Institute of General Medical Sciences (GM-08014, T32GM008014)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- SREBP pathway, SCAP, palmitic acid, fatty acid synthesis, sterol biosynthesis, isoprenoid biosynthesis, membrane integrity, cholesterol homeostasis, Drosophila, S2 cells, transcriptional regulation
- MeSH terms
- Animals, Cell Line, DNA-Binding Proteins, Drosophila, Fatty Acids, Humans, Membrane Proteins, Mutation, Peptide Fragments, Protein Processing, Post-Translational, RNA, Double-Stranded, RNA, Messenger, Sterols, Transcription Factors, Blotting, Western, Polymerase Chain Reaction, Sequence Homology, Amino Acid, Pyruvic Acid, Palmitic Acid, CCAAT-Enhancer-Binding Proteins, Intracellular Signaling Peptides and Proteins, Sterol Regulatory Element Binding Protein 1
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