The SREBP pathway in Drosophila: Regulation by palmitate, not sterols

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

Research output: Contribution to journalArticle

135 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalDevelopmental cell
Volume2
Issue number2
DOIs
StatePublished - Feb 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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