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Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter region
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Published/Copyright:
June 1, 2012
Abstract
The type II transmembrane serine protease matriptase-2 (TMPRSS6) down-regulates the expression of hepcidin, the main regulator of systemic iron homeostasis, and increases in this way iron plasma levels. Matriptase-2 is up-regulated under hypoxic conditions, providing a new link between hypoxia signaling and iron homeostasis. In this study, we have characterized the TMPRSS6 promoter region and identified a functional hypoxia-responsive element (HRE). Mutations of the hypoxia inducible factor (HIF)-binding site located within the HRE abrogate HIF-1α-dependent induction of TMPRSS6 expression. The action of HIF-1α on TMPRSS6 promoter activity reveals a new regulative element for the suppression of hepcidin synthesis.
Keywords: hepcidin; iron deficiency; reporter gene assay; transcriptional regulation; type II transmembrane serine protease
Received: 2011-9-22
Accepted: 2012-1-16
Published Online: 2012-06-01
Published in Print: 2012-06-01
©2012 by Walter de Gruyter Berlin Boston
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Keywords for this article
hepcidin;
iron deficiency;
reporter gene assay;
transcriptional regulation;
type II transmembrane serine protease
Articles in the same Issue
- Review
- The critical role of adrenomedullin and its binding protein, AMBP-1, in neuroprotection
- Minireview
- Ubiquilins in the crosstalk among proteolytic pathways
- Protein Structure and Function
- A non-cytotoxic but ribonucleolytically specific ribotoxin variant: implication of tryptophan residues in the cytotoxicity of hirsutellin A
- The composite nature of the interaction between nuclear receptors EcR and DHR38
- Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2
- New ketomethylene inhibitor analogues: synthesis and assessment of structural determinants for N-domain selective inhibition of angiotensin-converting enzyme
- Cadherin-related protein 24 induces morphological changes and partial cell polarization by facilitating direct cell-cell interactions
- Molecular Medicine
- Analysis of tissue and salivary nicotinamide N-methyltransferase in oral squamous cell carcinoma: basis for the development of a noninvasive diagnostic test for early-stage disease
- Cell Biology and Signaling
- Mitochondrial protein import pathways are functionally conserved among eukaryotes despite compositional diversity of the import machineries
- Small molecule inhibitors of the c-Jun N-terminal kinase (JNK) possess antiviral activity against highly pathogenic avian and human pandemic influenza A viruses
- Matriptase-2 (TMPRSS6) is directly up-regulated by hypoxia inducible factor-1: identification of a hypoxia-responsive element in the TMPRSS6 promoter region
- Rab1 interacts directly with the β2-adrenergic receptor to regulate receptor anterograde trafficking
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