Abstract |
A central means by which mammalian cells respond to low oxygen tension is through the activation of the transcription factor HIF-1 (hypoxia-inducible factor-1). Under normoxic conditions, HIF-1alpha (the alpha subunit of HIF-1) is targeted for rapid degradation by the ubiquitin- proteasome pathway. Under hypoxic conditions, this degradation is inhibited, thereby leading to the stabilization and activation of HIF-1alpha. Here, we report the identification of IOP1 ( iron-only hydrogenase-like protein 1), a protein homologous with enzymes present in anaerobic organisms that contain a distinctive iron- sulfur cluster. IOP1 is present in a broad range of cell types. Knockdown of IOP1 using siRNA ( small interfering RNA) in mammalian cells increases protein levels of HIF-1alpha under both normoxic and hypoxic conditions, and augments hypoxia-induced HRE ( hypoxia response element) reporter gene and endogenous HIF-1alpha target gene expressions. We find that IOP1 knockdown up-regulates HIF-1alpha mRNA levels, thereby providing a mechanism by which knockdown induces the observed effects. The results collectively provide evidence that IOP1 is a component of the protein network that regulates HIF-1alpha in mammalian cells.
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Authors | Jianhe Huang, Daisheng Song, Adrian Flores, Quan Zhao, Sharon M Mooney, Leslie M Shaw, Frank S Lee |
Journal | The Biochemical journal
(Biochem J)
Vol. 401
Issue 1
Pg. 341-52
(Jan 01 2007)
ISSN: 1470-8728 [Electronic] England |
PMID | 16956324
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- CIAO3 protein, human
- Iron-Sulfur Proteins
- Peptide Fragments
- Saccharomyces cerevisiae Proteins
- Hydrogenase
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Topics |
- Amino Acid Sequence
- Blotting, Northern
- Conserved Sequence
- Humans
- Hydrogenase
(chemistry, genetics, metabolism)
- Iron-Sulfur Proteins
- Kidney
- Molecular Sequence Data
- Peptide Fragments
(chemistry, metabolism)
- Saccharomyces cerevisiae
(enzymology)
- Saccharomyces cerevisiae Proteins
(chemistry, genetics, metabolism)
- Sequence Alignment
- Sequence Homology, Amino Acid
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