ArticleMolecular and cellular biology2008
Regulation of the Drosophila hypoxia-inducible factor alpha Sima by CRM1-dependent nuclear export.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Intratumor HIF-1α modulates production of a cachectic ligand to cause host wasting.Cell insight · 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
- Paths and pathways that generate cell-type heterogeneity and developmental progression in hematopoiesis.eLife · 2021Article
- The Discovery of Highly Potent THP Derivatives as OCTN2 Inhibitors: From Structure-Based Virtual Screening to In Vivo Biological Activity.International journal of molecular sciences · 2020Article
- The subcellular localization of bHLH transcription factor TCF4 is mediated by multiple nuclear localization and nuclear export signals.Scientific reports · 2019Article
- Article
- Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives.International journal of molecular sciences · 2019Review
- A Cell Density-Dependent Reporter in the Drosophila S2 Cells.Scientific reports · 2019Article
- Musashi mediates translational repression of the Drosophila hypoxia inducible factor.Nucleic acids research · 2016Article
- Structural and functional analysis of amphioxus HIFα reveals ancient features of the HIFα family.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Nicotinamide mononucleotide adenylyltransferase is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1alpha pathway.The Journal of biological chemistry · 2011Article
- Drosophila genome-wide RNAi screen identifies multiple regulators of HIF-dependent transcription in hypoxia.PLoS genetics · 2010Article
- Central role of the oxygen-dependent degradation domain of Drosophila HIFalpha/Sima in oxygen-dependent nuclear export.Molecular biology of the cell · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor alpha (HIF-alpha) proteins are regulated by oxygen levels through several different mechanisms that include protein stability, transcriptional coactivator recruitment, and subcellular localization. It was previously reported that these transcription factors are mainly nuclear in hypoxia and cytoplasmic in normoxia, but so far the molecular basis of this regulation is unclear. We show here that the Drosophila melanogaster HIF-alpha protein Sima shuttles continuously between the nucleus and the cytoplasm. We identified the relevant nuclear localization signal and two functional nuclear export signals (NESs). These NESs are in the Sima basic helix-loop-helix (bHLH) domain and promote CRM1-dependent nuclear export. Site-directed mutagenesis of either NES provoked Sima nuclear retention and increased transcriptional activity, suggesting that nuclear export contributes to Sima regulation. The identified NESs are conserved and probably functional in the bHLH domains of several bHLH-PAS proteins. We propose that rapid nuclear export of Sima regulates the duration of cellular responses to hypoxia.
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Registered trials
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