Journal article
Histone Deacetylase Inhibitors Induce VHL and Ubiquitin-Independent Proteasomal Degradation of Hypoxia-Inducible Factor 1α
Molecular and cellular biology, v 26(6), pp 2019-2028
Mar 2006
PMID: 16507982
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Adaptation to hypoxic microenvironment is critical for tumor survival and metastatic spread. Hypoxia-inducible factor 1α (HIF-1α) plays a key role in this adaptation by stimulating the production of proangiogenic factors and inducing enzymes necessary for anaerobic metabolism. Histone deacetylase inhibitors (HDACIs) produce a marked inhibition of HIF-1α expression and are currently in clinical trials partly based on their potent antiangiogenic effects. Although it has been postulated that HDACIs affect HIF-1α expression by enhancing its interactions with VHL (von Hippel Lindau), thus promoting its ubiquitination and degradation, the actual mechanisms by which HDACIs decrease HIF-1α levels are not clear. Here, we present data indicating that HDACIs induce the proteasomal degradation of HIF-1α by a mechanism that is independent of VHL and p53 and does not require the ubiquitin system. This degradation pathway involves the enhanced interaction of HIF-1α with HSP70 and is secondary to a disruption of the HSP70/HSP90 axis function that appears mediated by the activity of HDAC-6.
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Details
- Title
- Histone Deacetylase Inhibitors Induce VHL and Ubiquitin-Independent Proteasomal Degradation of Hypoxia-Inducible Factor 1α
- Creators
- Xianguo Kong - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Zhao Lin - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Dongming Liang - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Donna Fath - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Nianli Sang - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107Jaime Caro - Cardeza Foundation for Hematologic Research and Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
- Publication Details
- Molecular and cellular biology, v 26(6), pp 2019-2028
- Publisher
- American Society for Microbiology
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000235915400001
- Scopus ID
- 2-s2.0-33644780111
- Other Identifier
- 991014877858504721
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InCites Highlights
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology