ArticleMolecular and cellular biology2002
Control of the hypoxic response in Drosophila melanogaster by the basic helix-loop-helix PAS protein similar.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 251 citations in OpenAlex.
- Gut-derived Unpaired-3 cytokine signaling promotes systemic hypoxia tolerance in Drosophila.Disease models & mechanisms · 2026Article
- Emergence Biases in Molecular Evolution.Genome biology and evolution · 2026Review
- Gene model for the ortholog ofbioRxiv : the preprint server for biology · 2026Article
- Gene model for the ortholog ofbioRxiv : the preprint server for biology · 2026Article
- HIF-1α-mediated feedback prevents TOR signalling from depleting oxygen supply and triggering stress during normal development.Nature communications · 2025Article
- Gene model for the ortholog ofbioRxiv : the preprint server for biology · 2025Article
- Gene model for the ortholog ofbioRxiv : the preprint server for biology · 2025Article
- The translational inhibitor 4EBP/Thor is required for Drosophila adaptation to hypoxia.Scientific reports · 2025Article
- Hypoxia-inducible factor 1α is required to establish the larval glycolytic program in Drosophila melanogaster.Molecular metabolism · 2025Article
- Hypoxia-inducible factor 1α is required to establish the larval glycolytic program inbioRxiv : the preprint server for biology · 2025Article
- Gene model for the ortholog ofmicroPublication biology · 2025Article
- miR-210 is essential to retinal homeostasis in fruit flies and mice.Biology direct · 2024Article
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- Hypoxia delays steroid-induced developmental maturation in Drosophila by suppressing EGF signaling.PLoS genetics · 2024Article
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- Genetically Encoded Biosensors for the Fluorescence Detection of OSensors (Basel, Switzerland) · 2023Review
- Characterization of genetic and molecular tools for studying the endogenous expression ofbioRxiv : the preprint server for biology · 2023Article
- A FRET-based cGMP biosensor inmicroPublication biology · 2023Article
- Transcriptome analysis of FOXO-dependent hypoxia gene expression identifies Hipk as a regulator of low oxygen tolerance in Drosophila.G3 (Bethesda, Md.) · 2022Article
- M1-linked ubiquitination facilitates NF-κB activation and survival during sterile inflammation.The FEBS journal · 2022Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
In mammalian systems, the heterodimeric basic helix-loop-helix (bHLH)-PAS transcription hypoxia-inducible factor (HIF) has emerged as the key regulator of responses to hypoxia. Here we define a homologous system in Drosophila melanogaster, and we characterize its activity in vivo during development. By using transcriptional reporters in developing transgenic flies, we show that hypoxia-inducible activity rises to a peak in late embryogenesis and is most pronounced in tracheal cells. We show that the bHLH-PAS proteins Similar (Sima) and Tango (Tgo) function as HIF-alpha and HIF-beta homologues, respectively, and demonstrate a conserved mode of regulation for Sima by oxygen. Sima protein, but not its mRNA, was upregulated in hypoxia. Time course experiments following pulsed ectopic expression demonstrated that Sima is stabilized in hypoxia and that degradation relies on a central domain encompassing amino acids 692 to 863. Continuous ectopic expression overrode Sima degradation, which remained cytoplasmic in normoxia, and translocated to the nucleus only in hypoxia, revealing a second oxygen-regulated activation step. Abrogation of the Drosophila Egl-9 prolyl hydroxylase homologue, CG1114, caused both stabilization and nuclear localization of Sima, indicating a central involvement in both processes. Tight conservation of the HIF/prolyl hydroxylase system in Drosophila provides a new focus for understanding oxygen homeostasis in intact multicellular organisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.