Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice
Tumor hypoxia plays a crucial role in tumorigenesis. Under hypoxia, hypoxia-inducible factor 1α (HIF-1α) regulates activation of genes promoting malignant progression. Under normoxia, HIF-1α is hydroxylated on prolines 402 and 564 and is targeted for ubiquitin-mediated degradation by interacting wit...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2008-05-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2008.00017 |
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| Summary: | Tumor hypoxia plays a crucial role in tumorigenesis. Under hypoxia, hypoxia-inducible factor 1α (HIF-1α) regulates activation of genes promoting malignant progression. Under normoxia, HIF-1α is hydroxylated on prolines 402 and 564 and is targeted for ubiquitin-mediated degradation by interacting with the von Hippel-Lindau protein complex (pVHL). We have developed a novel method of studying the interaction between HIF-1α and pVHL using the split firefly luciferase complementation-based bioluminescence system in which HIF-1α and pVHL are fused to amino-terminal and carboxy-terminal fragments of the luciferase, respectively. We demonstrate that hydroxylation-dependent interaction between the HIF-1α and pVHL leads to complementation of the two luciferase fragments, resulting in bioluminescence in vitro and in vivo. Complementation-based bioluminescence is diminished when mutant pVHLs with decreased affinity for binding HIF-1α are used. This method represents a new approach for studying interaction of proteins involved in the regulation of protein degradation. |
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| ISSN: | 1536-0121 |