ArticleScientific reports2016
A novel injectable BRET-based in vivo imaging probe for detecting the activity of hypoxia-inducible factor regulated by the ubiquitin-proteasome system.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Bioluminescent Systems for Theranostic Applications.International journal of molecular sciences · 2024Review
- NanoBRET in C. elegans illuminates functional receptor interactions in real time.BMC molecular and cell biology · 2022Article
- In Vivo Imaging of Oxidative and Hypoxic Stresses in Mice Model of Amyotrophic Lateral Sclerosis.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Ways into Understanding HIF Inhibition.Cancers · 2021Review
- BRET based dual-colour (visible/near-infrared) molecular imaging using a quantum dot/EGFP-luciferase conjugate.RSC advances · 2019Article
- Chemiluminescence-initiated andChemical science · 2019Article
- A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries.Nature communications · 2018Article
- Novel adherent CD11bOncotarget · 2018Article
- Screening in larval zebrafish reveals tissue-specific distribution of fifteen fluorescent compounds.Disease models & mechanisms · 2017Article
- Luminescent Probe Based Techniques for Hypoxia Imaging.Journal of nanomedicine research · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The ubiquitin-proteasome system (UPS) is a selective protein degradation system that plays a critical role in many essential biological processes by regulating the existence of various cellular proteins. The target proteins of UPS are recognized and tagged with polyubiquitin chains by E3 ubiquitin ligases, which have high substrate-specific activities. Here we present a novel injectable imaging probe POL-N that can detect the UPS-regulated hypoxia-inducible factor (HIF) activity in vivo. Because the luciferase is fused to the E3 ligase-recognition domain of the HIF-1α, POL-N is intact only in the HIFα-overexpressing cells, that is, HIF-active cells, generating signals via an intramolecular bioluminescence resonance energy transfer (BRET) between luciferase and a near-infrared (NIR) fluorescent dye at the C-terminal end of the probe. Off-target signals of the NIR-BRET were so low that we could achieve highly sensitive and fast detection of intratumoral HIF-activity. Notably, we successfully detected hypoxic liver metastasis, which is extremely difficult to detect by injectable imaging probes due to strong off-target signals, as early as 1 h after systemic injection of POL-N. Our probe design can be widely adapted to UPS-target proteins and may contribute to the exploration of their roles in animal disease models.
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