Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster
Abstract
Mutation of members of the Halloween gene family results in embryonic lethality. We have shown that two of these genes code for enzymes responsible for specific steps in the synthesis of ecdysone, a polyhydroxylated sterol that is the precursor of the major molting hormone of all arthropods, 20-hydroxyecdysone. These two mitochondrial P450 enzymes, coded for by disembodied (dib) (CYP302A1) and shadow (sad) (CYP315A1), are the C22 and C2 hydroxylases, respectively, as shown by transfection of the gene into S2 cells and subsequent biochemical analysis. These are the last two enzymes in the ecdysone biosynthetic pathway. A third enzyme, necessary for the critical conversion of ecdysone to 20-hydroxyecdysone, the 20-monooxygenase, is encoded by shade (shd) (CYP314A1). All three enzymes are mitochondrial although shade has motifs suggesting both mitochondrial and microsomal locations. By tagging these enzymes, their subcellular location has been confirmed by confocal microscopy. Shade is present in several tissues as expected while disembodied and shadow are restricted to the ring gland. The paradigm used should allow us to define the enzymes mediating the entire ecdysteroid biosynthetic pathway.
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20E is an ecdysteroid hydroxylated at the 20th carbon in addition to other carbons.
“20E is an ecdysteroid hydroxylated at the 20th carbon in addition to other carbons [71].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [71]
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- Authors
- Gilbert, L. I.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Gilbert, Lawrence I
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 215
- Issue
- 1-2
- Pages
- 1-10
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W1971188096
- Cited by
- 300
- References
- 31
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 16 · 2023: 11 · 2022: 19 · 2021: 16 · 2020: 16 · 2019: 14 · 2018: 17 · 2017: 13 · 2016: 13 · 2015: 18 · 2014: 15 · 2013: 11 · 2012: 4
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- Halloween genes, ecdysone biosynthesis, 20-hydroxyecdysone, steroidogenesis, mitochondrial cytochrome P450, ring gland, Drosophila melanogaster, embryonic lethality, enzyme subcellular localization
- MeSH terms
- Animals, Cytochrome P-450 Enzyme System, Drosophila melanogaster, Ecdysone, Ecdysterone, Microsomes, Mitochondria, Gene Expression Regulation, Enzymologic, Drosophila Proteins
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