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
Publication statusPublished - May 2008

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ASJC Scopus subject areas

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

Cite this

Giaccia, A. J., Choi, C. Y. H., Chan, D. A., Paulmurugan, R., Sutphin, P. D., Le, Q. T., ... 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