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 |
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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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| _version_ | 1841561852091301888 |
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| author | Clara Y.H. Choi Denise A. Chan Ramasamy Paulmurugan Patrick D. Sutphin Quynh-Thu Le Albert C. Koong Wayne Zundel Sanjiv S. Gambhir Amato J. Giaccia |
| author_facet | Clara Y.H. Choi Denise A. Chan Ramasamy Paulmurugan Patrick D. Sutphin Quynh-Thu Le Albert C. Koong Wayne Zundel Sanjiv S. Gambhir Amato J. Giaccia |
| author_sort | Clara Y.H. Choi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-52906f6483cb4869a528cc85b4724323 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2008-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-52906f6483cb4869a528cc85b47243232025-01-03T01:22:54ZengSAGE PublishingMolecular Imaging1536-01212008-05-01710.2310/7290.2008.0001710.2310_7290.2008.00017Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in MiceClara Y.H. ChoiDenise A. ChanRamasamy PaulmuruganPatrick D. SutphinQuynh-Thu LeAlbert C. KoongWayne ZundelSanjiv S. GambhirAmato J. GiacciaTumor 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.https://doi.org/10.2310/7290.2008.00017 |
| spellingShingle | Clara Y.H. Choi Denise A. Chan Ramasamy Paulmurugan Patrick D. Sutphin Quynh-Thu Le Albert C. Koong Wayne Zundel Sanjiv S. Gambhir Amato J. Giaccia Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice Molecular Imaging |
| title | Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice |
| title_full | Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice |
| title_fullStr | Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice |
| title_full_unstemmed | Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice |
| title_short | Molecular Imaging of Hypoxia-Inducible Factor 1α and von Hippel-Lindau Interaction in Mice |
| title_sort | molecular imaging of hypoxia inducible factor 1α and von hippel lindau interaction in mice |
| url | https://doi.org/10.2310/7290.2008.00017 |
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