The serine protease TMPRSS6 is required to sense iron deficiency
| Autor: | Xin Du, Pauline Lee, Bruce Beutler, Terri Gelbart, Eva Marie Y Moresco, Jaroslav Truksa, Navjiwan Mann, Ernest Beutler, Kevin Khovananth, Yu Xia, Suzanne Mudd, Ellen She |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
TMPRSS6
Iron Mutant Mice Transgenic Transfection Models Biological Article Mice Hepcidins Hepcidin Cell Line Tumor Animals Humans Anemia Macrocytic Promoter Regions Genetic Hemojuvelin Regulation of gene expression Serine protease Multidisciplinary biology Serine Endopeptidases Membrane Proteins Iron Deficiencies Mice Mutant Strains Cell biology Protein Structure Tertiary Phenotype Biochemistry Gene Expression Regulation Mutation biology.protein HAMP Signal transduction Antimicrobial Cationic Peptides Signal Transduction |
| Popis: | Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask : a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6 . Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption. |
| Databáze: | OpenAIRE |
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