Molecular imaging of hypoxia-inducible factor 1α and von Hippel-Lindau interaction in mice

Amato J. Giaccia, Clara Y H Choi, Denise A. Chan, Ramasamy Paulmurugan, Patrick D. Sutphin, Quynh Thu Le, Albert C. Koong, Wayne Zundel, Sanjiv S. Gambhir

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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 ubiqultin-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-αa are used. This method represents a new approach for studying interaction of proteins involved in the regulation of protein degradation.

Original languageEnglish (US)
Pages (from-to)139-146
Number of pages8
JournalMolecular Imaging
Volume7
Issue number3
DOIs
StatePublished - May 2008

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging
  • Condensed Matter Physics

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    Giaccia, A. J., Choi, C. Y. H., Chan, D. A., Paulmurugan, R., Sutphin, P. D., Le, Q. T., Koong, A. C., Zundel, W., & Gambhir, S. S. (2008). Molecular imaging of hypoxia-inducible factor 1α and von Hippel-Lindau interaction in mice. Molecular Imaging, 7(3), 139-146. https://doi.org/10.2310/7290.2008.00017