Conditional inactivation of HIF-1 using intrabodies.

Conditional inactivation of HIF-1 using intrabodies. Cell Oncol. 2008;30(5):397-409 Authors: Groot AJ, Gort EH, van der Wall E, van Diest PJ, Vooijs M 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-1alpha 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. PMID: 18791271 [PubMed - indexed for MEDLINE]
Source: Analytical Cellular Pathology - Category: Cancer & Oncology Tags: Cell Oncol Source Type: research