Conditional inactivation of HIF-1 using intrabodies

Arjan J. Groot, Eelke H. Gort, Elsken Van Der Wall, Paul J. Van Diest, Marc Vooijs

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here we provide a novel approach for HIF-1 targeted therapy using single-domain llama antibodies directed against the HIF-1α oxygen dependent degradation domain which encompass the N-terminal transactivation domain. Conditional expression of HIF intrabodies in mammalian cells interfered with binding to pVHL and inhibited hypoxia induced activation of endogenous target genes. Inducible intrabody targeting is a highly specific strategy for temporal protein inactivation and may have applications for disease treatment.

Original languageEnglish (US)
Pages (from-to)397-409
Number of pages13
JournalCellular Oncology
Volume30
Issue number5
DOIs
StatePublished - Sep 30 2008

Keywords

  • Cancer
  • HIF
  • Hypoxia
  • Intrabody
  • Single-chain antibody fragment
  • VHH

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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