Open AccessConditional Inactivation of HIF-1 Using Intrabodies
Author(s) -
Arjan J. Groot,
Eelke Gort,
Elsken van der Wall,
Paul J. van Diest,
Marc Vooijs
Publication year - 2008
Publication title -
analytical cellular pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.576
H-Index - 24
eISSN - 2210-7185
pISSN - 2210-7177
DOI - 10.1155/2008/384945
Subject(s) - transactivation , transcription factor , regulator , hypoxia inducible factors , cancer research , hif1a , pas domain , endogeny , biology , hypoxia (environmental) , hypoxia inducible factor 1 , gene , microbiology and biotechnology , chemistry , genetics , biochemistry , angiogenesis , oxygen , organic chemistry
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-1 α 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.