Conditional Inactivation of HIF-1 Using Intrabodies
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 aggressive...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2008-01-01
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| Series: | Cellular Oncology |
| Online Access: | http://dx.doi.org/10.3233/CLO-2008-0442 |
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| _version_ | 1832545852009218048 |
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| author | Arjan J. Groot Eelke H. Gort Elsken van der Wall Paul J. van Diest Marc Vooijs |
| author_facet | Arjan J. Groot Eelke H. Gort Elsken van der Wall Paul J. van Diest Marc Vooijs |
| author_sort | Arjan J. Groot |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5c6e3f22de65459b9fbe9a703b8de21e |
| institution | Kabale University |
| issn | 1570-5870 1875-8606 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cellular Oncology |
| spelling | doaj-art-5c6e3f22de65459b9fbe9a703b8de21e2025-02-03T07:24:25ZengWileyCellular Oncology1570-58701875-86062008-01-0130539740910.3233/CLO-2008-0442Conditional Inactivation of HIF-1 Using IntrabodiesArjan J. Groot0Eelke H. Gort1Elsken van der Wall2Paul J. van Diest3Marc Vooijs4Department of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The NetherlandsDepartment of Internal Medicine, University Medical Center Utrecht, 3508 GA, Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The NetherlandsDepartment of Pathology, University Medical Center Utrecht, 3508 GA, Utrecht, The NetherlandsHypoxia 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.http://dx.doi.org/10.3233/CLO-2008-0442 |
| spellingShingle | Arjan J. Groot Eelke H. Gort Elsken van der Wall Paul J. van Diest Marc Vooijs Conditional Inactivation of HIF-1 Using Intrabodies Cellular Oncology |
| title | Conditional Inactivation of HIF-1 Using Intrabodies |
| title_full | Conditional Inactivation of HIF-1 Using Intrabodies |
| title_fullStr | Conditional Inactivation of HIF-1 Using Intrabodies |
| title_full_unstemmed | Conditional Inactivation of HIF-1 Using Intrabodies |
| title_short | Conditional Inactivation of HIF-1 Using Intrabodies |
| title_sort | conditional inactivation of hif 1 using intrabodies |
| url | http://dx.doi.org/10.3233/CLO-2008-0442 |
| work_keys_str_mv | AT arjanjgroot conditionalinactivationofhif1usingintrabodies AT eelkehgort conditionalinactivationofhif1usingintrabodies AT elskenvanderwall conditionalinactivationofhif1usingintrabodies AT pauljvandiest conditionalinactivationofhif1usingintrabodies AT marcvooijs conditionalinactivationofhif1usingintrabodies |