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The SREBP pathway in Drosophila: regulation by palmitate, not sterols.

Authors: Seegmiller, Adam C.; Dobrosotskaya, Irina; Goldstein, Joseph L.; Ho, Y.K.; Brown, Michael S.; Rawson, Robert B.;

The SREBP pathway in Drosophila: regulation by palmitate, not sterols.

Abstract

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.

Keywords

Sequence Homology, Amino Acid, Blotting, Western, Fatty Acids, Intracellular Signaling Peptides and Proteins, Palmitic Acid, Membrane Proteins, Polymerase Chain Reaction, Peptide Fragments, Cell Line, DNA-Binding Proteins, Mutation, Pyruvic Acid, CCAAT-Enhancer-Binding Proteins, Animals, Humans, Drosophila, RNA, Messenger, Sterol Regulatory Element Binding Protein 1, Protein Processing, Post-Translational, RNA, Double-Stranded

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
156
Top 10%
Top 10%
Top 1%